Structural highlights
FunctionPublication Abstract from PubMedD-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of L-amino acids into their D-counterparts is rare and chemically challenging. Bottromycins are ribosomally synthesized and post-translationally modified peptides that have overcome this challenge and feature a D-aspartate (D-Asp), which was proposed to arise spontaneously during biosynthesis. We have identified the highly unusual alpha/beta-hydrolase (ABH) fold enzyme BotH as a peptide epimerase responsible for the post-translational epimerization of L-Asp to D-Asp during bottromycin biosynthesis. The biochemical characterization of BotH combined with the structures of BotH and the BotH-substrate complex allowed us to propose a mechanism for this reaction. Bioinformatic analyses of BotH homologs show that similar ABH enzymes are found in diverse biosynthetic gene clusters. This places BotH as the founding member of a group of atypical ABH enzymes that may be able to epimerize non-Asp stereocenters across different families of secondary metabolites. The bottromycin epimerase BotH defines a group of atypical alpha/beta-hydrolase-fold enzymes.,Sikandar A, Franz L, Adam S, Santos-Aberturas J, Horbal L, Luzhetskyy A, Truman AW, Kalinina OV, Koehnke J Nat Chem Biol. 2020 Sep;16(9):1013-1018. doi: 10.1038/s41589-020-0569-y. Epub, 2020 Jun 29. PMID:32601484[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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