title: Characterization of Discrete Phosphopantetheinyl Transferases in Streptomyces tsukubaensis L19 Unveils a Complicate Phosphopantetheinylation Network.
abstract: Phosphopantetheinyl transferases (PPTases) play essential roles in both primary metabolisms and secondary metabolisms via post-translational modification of acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs). In this study, an industrial FK506 producing strain Streptomyces tsukubaensis L19, together with Streptomyces avermitilis, was identified to contain the highest number (five) of discrete PPTases known among any species thus far examined. Characterization of the five PPTases in S. tsukubaensis L19 unveiled that stw ACP, an ACP in a type II PKS, was phosphopantetheinylated by three PPTases FKPPT1, FKPPT3, and FKACPS; sts FAS ACP, the ACP in fatty acid synthase (FAS), was phosphopantetheinylated by three PPTases FKPPT2, FKPPT3, and FKACPS; TcsA-ACP, an ACP involved in FK506 biosynthesis, was phosphopantetheinylated by two PPTases FKPPT3 and FKACPS; FkbP-PCP, an PCP involved in FK506 biosynthesis, was phosphopantetheinylated by all of these five PPTases FKPPT1-4 and FKACPS. Our results here indicate that the functions of these PPTases complement each other for ACPs/PCPs substrates, suggesting a complicate phosphopantetheinylation network in S. tsukubaensis L19. Engineering of these PPTases in S. tsukubaensis L19 resulted in a mutant strain that can improve FK506 production.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Yue-Yue
authors.initials: YY
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Xiao-Sheng
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Hong-Dou
authors.initials: HD
authors.lastname: Luo
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Ni-Ni
authors.initials: NN
authors.lastname: Ren
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Xin-Hang
authors.initials: XH
authors.lastname: Jiang
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.|Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolism Engineering, Hangzhou, 310058, China.
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000213:Acyl Carrier Protein / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005285:Fermentation; D016680:Genome, Bacterial / Q000235:genetics; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D005810:Multigene Family; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism*
chemical_list: D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D002352:Carrier Proteins; C082662:phosphopantetheinyl transferase; D017855:Transferases (Other Substituted Phosphate Groups); D016559:Tacrolimus