6po6
MicroED Structure of a Natural Product VFAThiaGluMicroED Structure of a Natural Product VFAThiaGlu
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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