title: Biosynthetic Gene Cluster for Surugamide A Encompasses an Unrelated Decapeptide, Surugamide F.
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.
authors.affiliation: Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ninomiya
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Katsuyama
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, 060-0812, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kuranaga
authors.affiliation: Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Natsushima, Yokosuka, Kanagawa, 237-0061, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Natsushima, Yokosuka, Kanagawa, 237-0061, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nogi
authors.affiliation: Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Okada
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, 060-0812, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Wakimoto
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohnishi
authors.affiliation: Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan. assmats@mail.ecc.u-tokyo.ac.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan. atakada@mail.ecc.u-tokyo.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takada
mesh_terms: D005798:Genes, Bacterial / Q000235:genetics*; D008968:Molecular Conformation; D005810:Multigene Family / Q000235:genetics*; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics*
chemical_list: D010456:Peptides, Cyclic
keywords: Surugamide; biosynthesis; genome mining; natural products; peptides