Biosynthetic Gene Cluster for Surugamide A Encompasses an Unrelated Decapeptide, Surugamide F. (22nd July 2016)

• Record Type: Journal Article
• Authors: Ninomiya, Akihiro; Katsuyama, Yohei; Kuranaga, Takefumi; Miyazaki, Masayuki; Nogi, Yuichi; Okada, Shigeru; Wakimoto, Toshiyuki; Ohnishi, Yasuo; Matsunaga, Shigeki; Takada, Kentaro
• Is Part Of: Chembiochem. Volume 17:Number 18(2016)
• Page Start: 1709
• Page End: 1712
• Publication Date: 2016-07-22
• Subjects: biosynthesis -- genome mining -- natural products -- peptides -- Surugamide; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600350
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: 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. Abstract : The NRPS gene cluster for the cyclic octapeptide surugamide A was found in the draft genome sequence of Streptomyces sp. JAMM992. Genome mining and gene inactivation approaches revealed that the NRPS gene cluster was also responsible for the biosynthesis of a linear decapeptide, surugamide F. This study demonstrates that one NRPS cluster produces two unrelated classes of peptide.