title: Thiostrepton maturation involving a deesterification-amidation way to process the C-terminally methylated peptide backbone.
abstract: Thiopeptides are a class of clinically interesting and highly modified peptide antibiotics. Their biosyntheses share a common paradigm for characteristic core formation but differ in tailoring to afford individual members. Herein we report an unusual deesterification-amidation process in thiostrepton maturation to furnish the terminal amide moiety. TsrB, serving as a carboxylesterase, catalyzes the hydrolysis of the methyl ester intermediate to provide the carboxylate intermediate, which can be converted to the amide product by an amidotransferase, TsrC. These findings revealed a C-terminal methylation of the precursor peptide, which is cryptic in thiostrepton biosynthesis but potentially common in the formation of its homologous series of thiopeptides that vary in the C-terminal form as methyl ester, carboxylate, or amide.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Rijing
authors.initials: R
authors.lastname: Liao
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
mesh_terms: D000577:Amides / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D004951:Esterification; D008969:Molecular Sequence Data; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*; D013883:Thiostrepton / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D013883:Thiostrepton