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The bottromycin epimerase BotH defines a group of atypical α/β-hydrolase-fold enzymes.
Sikandar, Asfandyar Franz, Laura Adam, Sebastian Santos-Aberturas, Javier Horbal, Liliya Luzhetskyy, Andriy Truman, Andrew W Kalinina, Olga V Koehnke, Jesko
Sikandar, Asfandyar
Franz, Laura
Adam, Sebastian
Santos-Aberturas, Javier
Horbal, Liliya
Luzhetskyy, Andriy
Truman, Andrew W
Kalinina, Olga V
Koehnke, Jesko
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2020-06-29
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d-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 α/β-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.
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Nat Chem Biol. 2020 Jul 15;:]. Nat Chem Biol. 2020;16(9):1013-1018. doi:10.1038/s41589-020-0569-y.
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en
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1552-4469
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Attribution-NonCommercial-ShareAlike 4.0 International