title: Promiscuity of a modular polyketide synthase towards natural and non-natural extender units.
abstract: Combinatorial biosynthesis approaches that involve modular type I polyketide synthases (PKSs) are proven strategies for the synthesis of polyketides. In general however, such strategies are usually limited in scope and utility due to the restricted substrate specificity of polyketide biosynthetic machinery. Herein, a panel of chemo-enzymatically synthesized acyl-CoA's was used to probe the promiscuity of a polyketide synthase. Promiscuity determinants were dissected, revealing that the KS is remarkably tolerant to a diverse array of extender units, while the AT likely discriminates between extender units that are native to the producing organism. Our data provides a clear blueprint for future enzyme engineering efforts, and sets the stage for harnessing extender unit promiscuity by employing various in vivo polyketide diversification strategies.
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Koryakina
authors.forename: John B
authors.initials: JB
authors.lastname: McArthur
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Draelos
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Williams
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000737:chemistry / Q000378:metabolism; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012231:Rhizobium / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D048630:Polyketide Synthases; D003066:Coenzyme A Ligases; C021533:malonyl-CoA synthetase