6po6
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MicroED Structure of a Natural Product VFAThiaGlu
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Structural highlights
Publication Abstract from PubMedGenome sequencing of environmental bacteria allows identification of biosynthetic gene clusters encoding unusual combinations of enzymes that produce unknown natural products. We identified a pathway in which a ribosomally synthesized small peptide serves as a scaffold for nonribosomal peptide extension and chemical modification. Amino acids are transferred to the carboxyl terminus of the peptide through adenosine triphosphate and amino acyl-tRNA-dependent chemistry that is independent of the ribosome. Oxidative rearrangement, carboxymethylation, and proteolysis of a terminal cysteine yields an amino acid-derived small molecule. Microcrystal electron diffraction demonstrates that the resulting product is isosteric to glutamate. We show that a similar peptide extension is used during the biosynthesis of the ammosamides, which are cytotoxic pyrroloquinoline alkaloids. These results suggest an alternative paradigm for biosynthesis of amino acid-derived natural products. Use of a scaffold peptide in the biosynthesis of amino acid-derived natural products.,Ting CP, Funk MA, Halaby SL, Zhang Z, Gonen T, van der Donk WA Science. 2019 Jul 19;365(6450):280-284. doi: 10.1126/science.aau6232. PMID:31320540[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 10:38, 15 November 2023.