Sikandar_2020_Nat.Chem.Biol_16_1013

Reference

Title : The bottromycin epimerase BotH defines a group of atypical alpha\/beta-hydrolase-fold enzymes - Sikandar_2020_Nat.Chem.Biol_16_1013
Author(s) : Sikandar A , Franz L , Adam S , Santos-Aberturas J , Horbal L , Luzhetskyy A , Truman AW , Kalinina OV , Koehnke J
Ref : Nat Chemical Biology , 16 :1013 , 2020
Abstract :

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 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.

PubMedSearch : Sikandar_2020_Nat.Chem.Biol_16_1013
PubMedID: 32601484
Gene_locus related to this paper: 9actn-k4mhv9

Citations formats

Sikandar A, Franz L, Adam S, Santos-Aberturas J, Horbal L, Luzhetskyy A, Truman AW, Kalinina OV, Koehnke J (2020)
The bottromycin epimerase BotH defines a group of atypical alpha\/beta-hydrolase-fold enzymes
Nat Chemical Biology 16 :1013

Sikandar A, Franz L, Adam S, Santos-Aberturas J, Horbal L, Luzhetskyy A, Truman AW, Kalinina OV, Koehnke J (2020)
Nat Chemical Biology 16 :1013