title: Oxytetracycline biosynthesis improvement in Streptomyces rimosus following duplication of minimal PKS genes.
abstract: Oxytetracycline (OTC) is a widely used antibiotic, which is commercially produced by Streptomyces rimosus. The type II minimal polyketide synthases (minimal PKS) genes of the oxytetracycline biosynthesis cluster in S. rimosus, consisting of oxyA, oxyB and oxyC, are involved in catalyzing 19-C chain building by the condensation of eight malonyl-CoA groups to form the starting polyketide. This study aimed to investigate the effects of overexpression of the minimal PKS gene in a model S. rimosus strain (M4018) and in an industrial overproducer (SR16) by introduction of a second copy of the gene into the chromosome. Increased levels of oxyA, oxyB and oxyC gene transcription were monitored using reverse transcription quantitative real-time PCR. Overexpression of the minimal PKS gene elicited retardation of cell growth and a significant improvement in OTC production in corresponding mutants (approximately 51.2% and 32.9% in M4018 and SR16 mutants respectively). These data indicate that the minimal PKS plays an important role in carbon flux redirection from cell growth pathways to OTC biosynthesis pathways.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Nan
authors.initials: N
authors.lastname: Cao
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Ciying
authors.initials: C
authors.lastname: Xiao
authors.forename: Meijin
authors.initials: M
authors.lastname: Guo
authors.forename: Ju
authors.initials: J
authors.lastname: Chu
authors.forename: Yingping
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Siliang
authors.initials: S
authors.lastname: Zhang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001709:Biotechnology / Q000379:methods*; D020440:Gene Duplication; D005798:Genes, Bacterial; D005818:Genetic Engineering / Q000379:methods; D010118:Oxytetracycline / Q000096:biosynthesis*; D048630:Polyketide Synthases / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D048630:Polyketide Synthases; D010118:Oxytetracycline