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Biosynthetic Gene Cluster for SurugamideA Encompasses an Unrelated Decapeptide, SurugamideF

Genome mining is a powerful method for finding novel secondary metabolites. In our study on the biosynthetic gene cluster for the cyclic octapeptides surugamidesA-E (inhibitors of cathepsinB), we found a putative gene cluster consisting of four successive non-ribosomal peptide synthetase (NRPS) gene...

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Published in:Chembiochem : a European journal of chemical biology 2016-09, Vol.17 (18), p.1709-1712
Main Authors: Ninomiya, Akihiro, Katsuyama, Yohei, Kuranaga, Takefumi, Miyazaki, Masayuki, Nogi, Yuichi, Okada, Shigeru, Wakimoto, Toshiyuki, Ohnishi, Yasuo, Matsunaga, Shigeki, Takada, Kentaro
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Language:English
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Summary:Genome mining is a powerful method for finding novel secondary metabolites. In our study on the biosynthetic gene cluster for the cyclic octapeptides surugamidesA-E (inhibitors of cathepsinB), 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 surugamidesA-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, surugamideF. The pattern of intercalation observed in the sur genes is unprecedented. The structure of surugamideF, 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.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201600350