title: Pictet-Spenglerase involved in tetrahydroisoquinoline antibiotic biosynthesis.
abstract: Nonribosomal peptide synthetase (NRPS) is a programmable modular machinery that produces a number of biologically active small-molecule peptides. Saframycin A is a potent antitumor antibiotic with a unique pentacyclic tetrahydroisoquinoline scaffold. We found that the nonribosomal peptide synthetase SfmC catalyzes a seven-step transformation of readily synthesized dipeptidyl substrates with long acyl chains into a complex saframycin scaffold. Based on a series of enzymatic reactions, we proposed a detailed mechanism involving the reduction of various peptidyl thioesters by a single R domain followed by iterative C domain-mediated Pictet-Spengler reactions. This shows that NRPSs possess a remarkable capability to acquire novel function for diversifying structures of peptide natural products.
authors.affiliation: Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Koketsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Minami
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oguri
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oikawa
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D055162:Biocatalysis; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010447:Peptide Hydrolases / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D044005:Tetrahydroisoquinolines; D010447:Peptide Hydrolases