Radical S-Adenosyl Methionine Epimerases: Regioselective Introduction of Diverse D -Amino Acid Patterns into Peptide Natural Products
Résumé
PoyD is a radical S-adenosyl methionine epimerase that introduces multiple d-configured amino acids at alternating positions into the highly complex marine peptides poly-theonamide A and B. This novel post-translational modification contributes to the ability of the polytheonamides to form unimolecular minimalistic ion channels and its cytotoxic activity at picomolar levels. Using a genome mining approach we have identified additional PoyD homologues in various bacteria. Three enzymes were expressed in E. coli with their cognate as well as engineered peptide precursors and shown to introduce diverse d-amino acid patterns into all-l peptides. The data reveal a family of architecturally and functionally distinct enzymes that exhibit high regioselectivity, substrate promiscuity, and irreversible action and thus provide attractive opportunities for peptide engineering.
Domaines
Microbiologie et Parasitologie
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