6kji
Crystal structure of PsoF with SAH
Structural highlights
FunctionPSOF_ASPFU Dual-functional monooxygenase/methyltransferase; part of the gene cluster that mediates the biosynthesis of pseurotin A, a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation (PubMed:24082142, PubMed:24939566). The PKS-NRPS hybrid synthetase psoA is responsible for the biosynthesis of azaspirene, one of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142, PubMed:24939566). The dual-functional monooxygenase/methyltransferase psoF seems to be involved in the addition of the C3 methyl group onto the pseurotin scaffold (PubMed:24939566). Azaspirene is then converted to synerazol through 4 steps including oxidation of C17 by the cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group of C8 by the methyltransferase psoC, and the trans-to-cis isomerization of the C13 olefin by the glutathione S-transferase psoE (PubMed:24939566). The fourth step of synerazol production is performed by the dual-functional monooxygenase/methyltransferase psoF which seems to catalyze the epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566). Synerazol can be attacked by a water molecule nonenzymatically at two different positions to yield two diol products, pseurotin A and pseurotin D (PubMed:24939566).[1] [2] Publication Abstract from PubMedBiosynthesis of certain fungal polyketide-peptide synthetases involves C-methyltransferase activity that adds one or more S-adenosyl-l-methionine-derived methyl groups to the carbon framework. The previously reported PsoF-MT, the stand-alone C-methyltransferase (MT) from the pseurotin biosynthetic pathway that exists as a domain within a trifunctional didomain enzyme PsoF, was characterized crystallographically and kinetically using mutants with substrate analogs to understand how a trans-acting C-MT works and compare it to known polyketide synthase-associated C-MTs. This study identified key active-site residues involved in catalysis and substrate recognition, which led us to propose the mechanism of C-methylation and substrate specificity determinants in PsoF-MT. Functional and Structural Analyses of trans C-Methyltransferase in Fungal Polyketide Biosynthesis.,Kishimoto S, Tsunematsu Y, Matsushita T, Hara K, Hashimoto H, Tang Y, Watanabe K Biochemistry. 2019 Sep 24;58(38):3933-3937. doi: 10.1021/acs.biochem.9b00702., Epub 2019 Sep 11. PMID:31486637[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
