title: Identification of phoslactomycin biosynthetic gene clusters from Streptomyces platensis SAM-0654 and characterization of PnR1 and PnR2 as positive transcriptional regulators.
abstract: Phoslactomycins (PLMs) are inhibitors of protein serine/threonine phosphatase 2A showing diverse and important antifungal, antibacterial and antitumor activity. PLMs are polyketide natural products and produced by several Streptomyces species. The PLMs biosynthetic gene clusters were identified from Streptomyces platensis SAM-0654 and localized in two separate genomic regions, consisting of 27 open reading frames that encode polyketide synthases (PKSs), enzymes for cyclohexanecarboxyl-CoA (CHC-CoA) and ethylmalonyl-CoA (Em-CoA) synthesis, enzymes for post-PKS modifications, proposed regulators, and putative resistance transporters. Bioinformatic analysis and inactivation experiment of regulatory genes suggest that PnR1 and PnR2 are two positive regulators of PLMs biosynthesis. Gene transcription analysis by reverse transcriptase PCR (RT-PCR) of the PLMs gene cluster demonstrated that PnR1 and PnR2 activate the transcription of the structural biosynthetic genes while PnR2 specially governs the transcription of pnR1 in a higher level.
authors.affiliation: State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Yun-Liang
authors.initials: YL
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Gao
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Tao
authors.forename: Hai-Xue
authors.initials: HX
authors.lastname: Pan
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tang
mesh_terms: D000214:Acyl Coenzyme A / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial; D007783:Lactones / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames; D009943:Organophosphorus Compounds / Q000378:metabolism; D010802:Phylogeny; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D011753:Pyrones; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D007783:Lactones; D009943:Organophosphorus Compounds; D011753:Pyrones; D012333:RNA, Messenger; C102829:ethylmalonyl-coenzyme A; C060448:phoslactomycin A; C046663:cyclohexanecarboxyl-coenzyme A; D048630:Polyketide Synthases