title: Improvement of natamycin production by engineering of phosphopantetheinyl transferases in Streptomyces chattanoogensis L10.
abstract: Phosphopantetheinyl transferases (PPTases) are essential to the activities of type I/II polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) through converting acyl carrier proteins (ACPs) in PKSs and peptidyl carrier proteins (PCPs) in NRPSs from inactive apo-forms into active holo-forms, leading to biosynthesis of polyketides and nonribosomal peptides. The industrial natamycin (NTM) producer, Streptomyces chattanoogensis L10, contains two PPTases (SchPPT and SchACPS) and five PKSs. Biochemical characterization of these two PPTases shows that SchPPT catalyzes the phosphopantetheinylation of ACPs in both type I PKSs and type II PKSs, SchACPS catalyzes the phosphopantetheinylation of ACPs in type II PKSs and fatty acid synthases (FASs), and the specificity of SchPPT is possibly controlled by its C terminus. Inactivation of SchPPT in S. chattanoogensis L10 abolished production of NTM but not the spore pigment, while overexpression of the SchPPT gene not only increased NTM production by about 40% but also accelerated productions of both NTM and the spore pigment. Thus, we elucidated a comprehensive phosphopantetheinylation network of PKSs and improved polyketide production by engineering the cognate PPTase in bacteria.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Yue-Yue
authors.initials: YY
authors.lastname: Wang
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Ran
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Fan
authors.forename: Xin-Hang
authors.initials: XH
authors.lastname: Jiang
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Guan
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D057005:Bioengineering; D019149:Bioreactors; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010866:Natamycin / Q000096:biosynthesis*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C082662:phosphopantetheinyl transferase; D010866:Natamycin; D017855:Transferases (Other Substituted Phosphate Groups)