title: Identification and Characterization of the Streptazone E Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08.
abstract: Streptazone derivatives isolated from Streptomyces species are piperidine alkaloids with a cyclopenta[b]pyridine scaffold. Previous studies indicated that these compounds are polyketides, but the biosynthetic enzymes responsible for their synthesis are unknown. Here, we have identified the streptazone E biosynthetic gene cluster in Streptomyces sp. MSC090213JE08, which encodes a modular type I PKS and tailoring enzymes that include an aminotransferase, three oxidoreductases, and two putative cyclases. The functions of the six tailoring enzymes were analyzed by gene disruption, and two putative biosynthetic intermediates that accumulated in particular mutants were structurally elucidated. On the basis of these results, we propose a pathway for the biosynthesis of streptazone E in which the two putative cyclases of the nuclear transport factor 2-like superfamily are responsible for C-C bond formation coupled with epoxide ring opening to give the five-membered ring of streptazone E.
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: Shoto
authors.initials: S
authors.lastname: Ohno
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: Yuka
authors.initials: Y
authors.lastname: Tajima
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: 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: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, 904-0495, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujie
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, 904-0495, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Satoh
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. ayasuo@mail.ecc.u-tokyo.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohnishi
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D008190:Lyases / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D005810:Multigene Family; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D048630:Polyketide Synthases / Q000378:metabolism; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000637:Transaminases / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010880:Piperidines; D061065:Polyketides; C582408:streptazone E; D048630:Polyketide Synthases; D010088:Oxidoreductases; D000637:Transaminases; D008190:Lyases
keywords: Streptomyces; biosynthesis; cyclases; polyketides; streptazone E