| Autor: |
Sikandar, Asfandyar, Franz, Laura, Adam, Sebastian, Santos-Aberturas, Javier, Horbal, Liliya, Luzhetskyy, Andriy, Truman, Andrew W., Kalinina, Olga V., Koehnke, Jesko |
| Zdroj: |
Nature Chemical Biology; September 2020, Vol. 16 Issue: 9 p1013-1018, 6p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
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