2024-03-29T13:07:11Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/810302024-02-15T08:02:10Zhdl_2115_20045hdl_2115_139Identification of the peptide epimerase MslH responsible for d-amino acid introduction at the C-terminus of ribosomal peptidesFeng, ZhiOgasawara, YasushiDairi, TohruA 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 C-alpha 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.Royal Society of ChemistryJournal Articlehttp://hdl.handle.net/2115/810302041-6520Chemical science127256725742021-02-21enginfo:doi/10.1039/d0sc06308hnone