title: Construction of a bacterial artificial chromosome library for a myxobacterium of the genus Cystobacter and characterization of an antibiotic biosynthetic gene cluster.
abstract: A bacterial artificial chromosome (BAC) library was constructed to isolate the biosynthetic gene cluster for the polyketide/peptide hybrid-type antibiotic cystothiazole A from the myxobacterium Cystobacter fuscus strain AJ-13278. Sequence analysis of a 63.9 kb contiguous region that encompasses the biosynthetic gene cluster (cta) led to the identification of a polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid gene cluster 32.1 kb in size, which consists of six open reading frames (ORFs), ctaB to ctaG, as well as downstream genes ctaJ and ctaK (1.0 and 0.9 kb, respectively) responsible for the final biosynthetic steps. The genes ctaB, ctaE, and ctaF encode PKSs, the genes ctaC and ctaG encode NRPSs, and ctaD encodes an NRPS-PKS hybrid enzyme. Disruption of ctaD impaired cystothiazole A production. Additionally, two downstream genes, ctaJ and ctaK, which encode a nitrilase and an O-methyltransferase, respectively, must be responsible for the final methyl ester formation in the cystothiazole A biosynthesis.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chukusa-ku, Nagoya 464-8601, Japan.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Feng
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qi
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuge
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oba
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Youji
authors.initials: Y
authors.lastname: Sakagami
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D023061:Gene Order; D005798:Genes, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics*; D009231:Myxococcales / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D013844:Thiazoles; C112182:cystothiazole A; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase