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Biosynthetic Gene Cluster for Surugamide A Encompasses an Unrelated Decapeptide, Surugamide F
Author(s) -
Ninomiya Akihiro,
Katsuyama Yohei,
Kuranaga Takefumi,
Miyazaki Masayuki,
Nogi Yuichi,
Okada Shigeru,
Wakimoto Toshiyuki,
Ohnishi Yasuo,
Matsunaga Shigeki,
Takada Kentaro
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600350
Subject(s) - gene cluster , gene , peptide , biosynthesis , amino acid , biochemistry , biology , genetics , genome , stereochemistry , chemistry
Genome mining is a powerful method for finding novel secondary metabolites. In our study on the biosynthetic gene cluster for the cyclic octapeptides surugamides A–E (inhibitors of cathepsin B), we found a putative gene cluster consisting of four successive non‐ribosomal peptide synthetase (NRPS) genes, surA , surB , surC , and surD . Prediction of amino acid sequence based on the NRPSs and gene inactivation revealed that surugamides A–E are produced by two NRPS genes, surA and surD , which were separated by two NRPS genes, surB and surC . The latter genes are responsible for the biosynthesis of an unrelated peptide, surugamide F. The pattern of intercalation observed in the sur genes is unprecedented. The structure of surugamide F, a linear decapeptide containing one 3‐amino‐2‐methylpropionic acid (AMPA) residue, was determined by spectroscopic methods and was confirmed by solid‐phase peptide synthesis.