https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Lisa+M.+LeoneProteopedia - User contributions [en]2026-09-24T12:11:29ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1340115User:Lisa M. Leone/Sandbox 12012-01-04T17:20:11Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
== Taxol Carbon Skeleton ==<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
== Taxol side-chain ==<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='PAM'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1340114User:Lisa M. Leone/Sandbox 12012-01-04T17:19:41Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
== Taxol Carbon Skeleton ==<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
== Taxol side-chain ==<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='PAM'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1340113User:Lisa M. Leone/Sandbox 12012-01-04T17:18:52Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
=== Taxol Carbon Skeleton ===<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
<br />
<br />
<br />
<br />
=== Taxol side-chain ===<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='PAM'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339248User:Lisa M. Leone/Sandbox 12012-01-03T21:59:19Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
=== Taxol Carbon Skeleton ===<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
=== Taxol side-chain ===<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='PAM'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339247User:Lisa M. Leone/Sandbox 12012-01-03T21:56:44Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
=== Taxol Carbon Skeleton ===<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
=== Taxol side-chain ===<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339246User:Lisa M. Leone/Sandbox 12012-01-03T21:53:22Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
=== Taxol Carbon Skeleton ===<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
= Taxol side-chain =<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339245User:Lisa M. Leone/Sandbox 12012-01-03T21:52:53Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
= Taxol Carbon Skeleton =<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
= Taxol side-chain =<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339244User:Lisa M. Leone/Sandbox 12012-01-03T21:50:41Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
== Taxol Carbon Skeleton ==<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='300' frame='true' align='left' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<Structure load='3p5r' size='300' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
== Taxol side-chain ==<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339243User:Lisa M. Leone/Sandbox 12012-01-03T21:47:42Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
<br />
== Taxol Carbon Skeleton ==<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
<br />
== Taxol side-chain ==<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339242User:Lisa M. Leone/Sandbox 12012-01-03T21:46:29Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
Taxol Carbon Skeleton:<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5Aol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
Taxol side-chain:<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339241User:Lisa M. Leone/Sandbox 12012-01-03T21:45:36Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''. Taxol is synthesized ''in planta'' as a secondary metabolite. Secondary metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of protection against insects and disease. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
Taxol Carbon Skeleton:<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene> --> Unknown steps --> <scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene> --> <scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene> --> Paclitaxel<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='TXS' /><br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is <scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='TXS'>Taxadiene Synthase (TXS)</scene>, a lyase enzyme. TXS's crystal structure has recently been published. TXS's <scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='TXS'>active site</scene> relies on Mg2+ metal chemistry to catalyze the reaction. (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The Taxol biosynthetic pathway comprises approximately 20 steps in total, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). <br />
<br />
Taxol side-chain:<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Phenylalanine Aminomutase (PAM)' scene='User:Lisa_M._Leone/Sandbox_1/Pam/1' name='PAM' /><br />
<br />
A modified phenylalanine side chain is added to the Taxol carbon skeleton (Baccatin III) late in the pathway. The first dedicated step of this side-chain pathway is the isomerization of phenylalanine, catalyzed by <scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene>. PAM's crystal structure has also recently been published. PAM's <scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2' target='PAM'>active site</scene> relies on a 4-methylidene-1H-imidazol-5(4H)-one prosthesis characteristic of the class I lyase family. citation: <br />
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase<br />
Lei Feng, Udayanga Wanninayake, Susan Strom, James Geiger, and Kevin D. Walker<br />
Biochemistry 2011 50 (14), 2919-2930</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339228User:Lisa M. Leone/Sandbox 12012-01-03T15:55:35Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/2'>PAMActiveSite</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene><br />
<br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1339227User:Lisa M. Leone/Sandbox 12012-01-03T15:42:42Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Pamactivesite/1'>PAMActiveSite</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene><br />
<br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338604User:Lisa M. Leone/Sandbox 12011-12-30T22:30:04Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Pam/1' target='proteins'>Phenylalanine aminomutase (PAM)</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene><br />
<br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338603User:Lisa M. Leone/Sandbox 12011-12-30T22:25:36Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/10deacetylbaccatin3/1' target='metabolites'>10-deacetylbaccatinIII</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene><br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338602User:Lisa M. Leone/Sandbox 12011-12-30T22:22:08Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Baccatiniii/1' target='metabolites'>BaccatinIII</scene><br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338600User:Lisa M. Leone/Sandbox 12011-12-30T22:18:58Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene><br />
<br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338599User:Lisa M. Leone/Sandbox 12011-12-30T22:17:56Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/1' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/3' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/2' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/2' target='metabolites'>Taxa411dien5αol</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5a13aol/1' target='metabolites'>Taxa411dien5A13Aol</scene><br />
<br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338597User:Lisa M. Leone/Sandbox 12011-12-30T22:00:54Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='User:Lisa_M._Leone/Sandbox_1/Ggpp/' size='500' frame='true' align='right' caption='Intermediates in the Taxol Pathway' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/1' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/2' target='metabolites'>Geranylgeranyl diphosphate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411diene/1' target='metabolites'>Taxa-4,11-diene</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxa411dien5aol/1'>Taxa 4 11 dien 5α ol</scene><br />
<br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338592User:Lisa M. Leone/Sandbox 12011-12-30T21:45:59Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
Add to Taxol discussion - stabilization of tubulin sheet by taxol: PDB ref IJFF : http://www.pdb.org/pdb/explore/explore.do?structureId=1JFF<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
Molecular scene 1 - slideshow of metabolites in main structure: taxa-4,11-diene, taxa-4,11-dien-5A-ol, Taxa-4,11-dien 5A 13A diol, 10-deacetyl baccatin III, baccatin III, (side chain), 3,N-debenzoyl Taxol, paclitaxel<br />
Molecular scene 2 - side-chain, Phenylalanine, beta phenylalanine, phenylisoserine<br />
<br />
Proteins: taxadiene synthase(3p5r), tcPAM (3nz4)(lyase, catalyzes 1st dedicated step of side chain pathway), phenyalanine aminomutase(2yii) (http://www.pdb.org/pdb/explore/explore.do?structureId=2YII)<br />
<br />
Proteins:<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
Metabolites:<br />
<br />
<Structure load='Methyl_jasmonate/1' size='500' frame='true' align='right' caption='Insert caption here' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/1' name='metabolites' /><br />
<br />
<br />
<br />
new scene (active site)<br />
<br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/1' target='metabolites'>Geranylgeranyl Diphosphate (GGPP)</scene><br />
<br />
Other:<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:Taxa_4_11_diene.pdb&diff=1338591File:Taxa 4 11 diene.pdb2011-12-30T21:45:36Z<p>Lisa M. Leone: Taxa-4,11-diene is an intermediate in the taxol pathway. Structure data from NCBI compound database.</p>
<hr />
<div>Taxa-4,11-diene is an intermediate in the taxol pathway. Structure data from NCBI compound database.</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:Taxa_4_11_dien_5A_13A_diol.pdb&diff=1338590File:Taxa 4 11 dien 5A 13A diol.pdb2011-12-30T21:41:29Z<p>Lisa M. Leone: Taxa-4,11-dien 5A 13A diol is an intermediate in the taxol pathway. Structure from NCBI compound database.</p>
<hr />
<div>Taxa-4,11-dien 5A 13A diol is an intermediate in the taxol pathway. Structure from NCBI compound database.</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:Taxa_4_11_dien_5_alpha_ol.pdb&diff=1338589File:Taxa 4 11 dien 5 alpha ol.pdb2011-12-30T21:40:48Z<p>Lisa M. Leone: Taxa-4,11-dien 5A ol is an intermediate in the taxol pathway. Structure from NCBI compound database.</p>
<hr />
<div>Taxa-4,11-dien 5A ol is an intermediate in the taxol pathway. Structure from NCBI compound database.</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:10deacetyl_baccatin_3.pdb&diff=1338587File:10deacetyl baccatin 3.pdb2011-12-30T21:39:56Z<p>Lisa M. Leone: 10 deacetyl baccatin III is the precursor to baccatin III intermediate for taxol page</p>
<hr />
<div>10 deacetyl baccatin III is the precursor to baccatin III intermediate for taxol page</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:3_N_debenzoyl_Taxol.pdb&diff=1338585File:3 N debenzoyl Taxol.pdb2011-12-30T21:39:18Z<p>Lisa M. Leone: 3N debenzoyl taxol intermediate metabolite for taxol page</p>
<hr />
<div>3N debenzoyl taxol intermediate metabolite for taxol page</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338568User:Lisa M. Leone/Sandbox 12011-12-30T20:56:43Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
<br />
<br />
<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' name='proteins' /><br />
<br />
<Structure load='Methyl_jasmonate/1' size='500' frame='true' align='right' caption='Insert caption here' scene='User:Lisa_M._Leone/Sandbox_1/Ggpp/1' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/1' target='metabolites'>Geranylgeranyl Diphosphate (GGPP)</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:Baccattin_3.pdb&diff=1338567File:Baccattin 3.pdb2011-12-30T20:56:26Z<p>Lisa M. Leone: Baccatin III for taxol page</p>
<hr />
<div>Baccatin III for taxol page</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338562User:Lisa M. Leone/Sandbox 12011-12-30T20:46:23Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<br />
== Taxol Biosynthesis ==<br />
<br />
Taxol is a complex diterpenoid produced mainly in the bark of the yew tree, genus ''Taxus''.<br />
<br />
<br />
Taxol is produced ''in planta'' as a secondary metabolite. These metabolites are produced in small quantities and are thought to provide an evolutionary benefit for plants in terms of insect or disease protection. In cell suspension cultures, Taxol is produced in very small quantities basally, but when an elicitor is added to the media Taxol production rises dramatically. A common elicitor is methyl jasmonate (MJ), a plant hormone known to activate plant defense pathways in many species. Among other things, MJ activates a cascade resulting in expression of taxol biosynthesis proteins and re-routing of primary metabolism into secondary metabolism.<br />
<br />
The first dedicated step of the Taxol biosynthetic pathway is the conversion of geranylgeranyl diphosphate (GGPP), the precursor for all plant diterpenoids, into taxa-4,11-diene. The enzyme catalyzing the conversion of GGPP is taxadiene synthase (TXS), a lyase enzyme. Because TXS relies on Mg2+ metal chemistry to catalyze the reaction it is classified as a class I terpenoid cyclase (citation: Mustafa Köksal, Yinghua Jin, Robert M. Coates, Rodney Croteau & David W. Christianson Nature 469, 116–120 (06 January 2011) doi:10.1038/nature09628)<br />
<br />
The remainder of the Taxol biosynthetic pathway comprises approximately 20 steps, of which a few remain unknown. Efforts are currently underway in the Roberts, Walker and Normanly labs to identify the enzyme catalyzing the formation of the oxetane ring moiety in Taxol, which has been shown to be essential for its microtubule binding activity (citation: Expositio taxol paper). The known steps of the Taxol biosynthetic pathway can be seen in Figure X. <br />
<br />
<br />
<br />
<br />
<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' name='proteins' /><br />
<br />
<Structure load='Methyl_jasmonate/1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' name='metabolites' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2' target='proteins'>Taxadiene Synthase (TXS)</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1' target='proteins'>TXS Active Site</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1' target='metabolites'>Methyl Jasmonate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/1' target='metabolites'>Geranylgeranyl Diphosphate (GGPP)</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338531User:Lisa M. Leone/Sandbox 12011-12-30T19:16:22Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' /><br />
<br />
<Structure load='Methyl_jasmonate/1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2'>Taxadiene Synthase (TXS)</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1'>TXS Active Site</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1'>Methyl Jasmonate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/1'>Geranylgeranyl Diphosphate (GGPP)</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338530User:Lisa M. Leone/Sandbox 12011-12-30T19:05:02Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' /><br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2'>Taxadiene Synthase (TXS)</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1'>TXS Active Site</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1'>Methyl Jasmonate</scene><br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Ggpp/1'>Geranylgeranyl Diphosphate (GGPP)</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:Ggpp_pdb_2.pdb&diff=1338525File:Ggpp pdb 2.pdb2011-12-30T18:58:15Z<p>Lisa M. Leone: Geranygeranyl diphosphate (GGPP) pdb structure for taxol page</p>
<hr />
<div>Geranygeranyl diphosphate (GGPP) pdb structure for taxol page</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338523User:Lisa M. Leone/Sandbox 12011-12-30T18:50:36Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' /><br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2'>Taxadiene Synthase (TXS)</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1'>TXS Active Site</scene><br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Methyl_jasmonate/1'>Methyl Jasmonate</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338522User:Lisa M. Leone/Sandbox 12011-12-30T18:43:05Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' /><br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/2'>Taxadiene Synthase (TXS)</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1'>TXS Active Site</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338521User:Lisa M. Leone/Sandbox 12011-12-30T18:42:34Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' /><br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/1'>Taxadiene Synthase (TXS)</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1'>TXS Active Site</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338520User:Lisa M. Leone/Sandbox 12011-12-30T18:39:40Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' /><br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/1'>TextToBeDisplayed</scene><br />
<br />
new scene (active site)<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Active_site_taxadiene_synthase/1'>TextToBeDisplayed</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338512User:Lisa M. Leone/Sandbox 12011-12-30T17:56:08Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<Structure load='3p5r' size='500' frame='true' align='right' caption='Taxadiene synthase' scene='spinning' /><br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/1'>TextToBeDisplayed</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338511User:Lisa M. Leone/Sandbox 12011-12-30T17:52:20Z<p>Lisa M. Leone: </p>
<hr />
<div>This is my sandbox<br />
<br />
<br />
<scene name='User:Lisa_M._Leone/Sandbox_1/Taxadiene_synthase/1'>TextToBeDisplayed</scene></div>Lisa M. Leonehttps://proteopedia.org/index.php?title=File:Jasmonic_acid.pdb&diff=1338510File:Jasmonic acid.pdb2011-12-30T17:44:14Z<p>Lisa M. Leone: Jasmonic Acid structure for use on Taxol page</p>
<hr />
<div>Jasmonic Acid structure for use on Taxol page</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone/Sandbox_1&diff=1338449User:Lisa M. Leone/Sandbox 12011-12-30T16:35:32Z<p>Lisa M. Leone: New page: This is my sandbox</p>
<hr />
<div>This is my sandbox</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone&diff=1338448User:Lisa M. Leone2011-12-30T16:34:59Z<p>Lisa M. Leone: </p>
<hr />
<div>*Chemical Engineering Graduate Student, Sue Roberts Lab<br />
*University of Massachusetts, Amherst, USA<br />
<br />
*[[User:Lisa M. Leone/Sandbox 1]]</div>Lisa M. Leonehttps://proteopedia.org/index.php?title=User:Lisa_M._Leone&diff=1338447User:Lisa M. Leone2011-12-30T16:34:27Z<p>Lisa M. Leone: </p>
<hr />
<div>*Chemical Engineering Graduate Student, Sue Roberts Lab<br />
*University of Massachusetts, Amherst, USA<br />
<br />
*[[User:Your Name/Sandbox 1]]</div>Lisa M. Leone