Identification of the peptide epimerase MslH responsible for d-amino acid introduction at the C-terminus of ribosomal peptides |
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Authors: | Zhi Feng Yasushi Ogasawara Tohru Dairi |
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Affiliation: | Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo Hokkaido 060-8628 Japan ; Graduate School of Engineering, Hokkaido University, Sapporo Hokkaido 060-8628 Japan, |
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Abstract: | A lasso peptide MS-271 is a ribosomally synthesized and post-translationally modified peptide (RiPP) consisting of 21 amino acids with a d-tryptophan (Trp) at its C terminus. The presence of d-amino acids is rare in RiPPs and few mechanisms of d-amino acid introduction have been characterized. Here, we report the identification of MslH, previously annotated as a hypothetical protein, as a novel epimerase involved in the post-translational epimerization of the C-terminal Trp residue of the precursor peptide MslA. MslH is the first epimerase that catalyzes epimerization at the Cα center adjacent to a carboxylic acid in a cofactor-independent manner. We also demonstrate that MslH exhibits broad substrate specificity toward the N-terminal region of the core peptide, showing that MslH-type epimerases offer opportunities in peptide bioengineering.The biosynthesis of d-tryptophan containing lasso peptide MS-271 involves the epimerization of a ribosomal peptide MslA catalyzed by a novel class of metal- and cofactor-independent peptide epimerase MslH. |
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