title: Biosynthesis of the 4-methyloxazoline-containing nonribosomal peptides, JBIR-34 and -35, in Streptomyces sp. Sp080513GE-23.
abstract: JBIR-34 and -35 produced by Streptomyces sp. Sp080513GE-23 are nonribosomal peptides that possess an unusual 4-methyloxazoline moiety. Through draft genome sequencing, cosmid cloning, and gene disruption, the JBIR-34 and -35 biosynthesis gene cluster (fmo cluster) was identified; it encodes 20 proteins including five nonribosomal peptide synthetases (NRPSs). Disruption of one of these NRPS genes (fmoA3) resulted in no JBIR-34 and -35 production and accumulation of 6-chloro-4-hydroxyindole-3-carboxylic acid. Stable isotope-feeding experiments indicated that the methyl group of the methyloxazoline ring is derived from alanine rather than methionine. A recombinant FmoH protein, a glycine/serine hydroxymethyltransferase homolog, catalyzed conversion of α-methyl-l-serine into d-alanine (the reverse reaction of α-methyl-l-serine synthesis catalyzed by FmoH in vivo). Taken together, we concluded that α-methyl-l-serine synthesized from d-alanine is incorporated into JBIR-34 and -35 to form the 4-methyloxazoline moiety. We also propose the biosynthesis pathway of JBIR-34 and -35.
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Adeline
authors.initials: A
authors.lastname: Muliandi
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Katsuyama
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sone
authors.affiliation: Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Izumikawa
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Moriya
authors.affiliation: Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hashimoto
authors.affiliation: Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kozone
authors.affiliation: Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Takagi
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-ya
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Electronic address: ayasuo@mail.ecc.u-tokyo.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohnishi
mesh_terms: D007211:Indoles / Q000737:chemistry; D015394:Molecular Structure; D009842:Oligopeptides / Q000096:biosynthesis* / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry* / Q000378:metabolism; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D007211:Indoles; C548191:JBIR-34; C548192:JBIR-35; D009842:Oligopeptides; D010080:Oxazoles