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Updated: May 24, 2026

Synthesis and Assay of Vibrio Quorum Sensing Inhibitors
Published on: May 31, 2024
Pictet-Spenglerase involved in tetrahydroisoquinoline antibiotic biosynthesis
Kento Koketsu1, Atsushi Minami, Kenji Watanabe
1Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
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.
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