Improvement of Natamycin Production by Engineering of Phosphopantetheinyl Transferases in Streptomyces chattanoogensis L10

Phosphopantetheinyl transferases (PPTases) are essential to the activities of type I/II polyketide synthases (PKSs) and non ribosomal 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 non ribosomal 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: 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); 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 SchPPT not only increased the 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 the polyketide production by engineering the cognate PPTase in bacteria.

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