title: Exploiting the reaction flexibility of a type III polyketide synthase through in vitro pathway manipulation.
abstract: A synthetic metabolic pathway has been constructed in vitro consisting of the type III polyketide synthase from Streptomyces coelicolor and peroxidases from soybean and Caldariomyces fumago (chloroperoxidase). This has resulted in the synthesis of the pentaketide flaviolin and its dimeric derivative, and a wide range of pyrones and their coupled derivatives with flaviolin, as well as their halogenated derivatives. The addition of acyl-CoA oxidase to the pathway prior to the polyketide synthase resulted in unsaturated pyrone side chains, further broadening the product spectrum that can be achieved. The approach developed in this work, therefore, provides a new model to exploit biocatalysis in the synthesis of complex natural product derivatives.
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Jae-Cheol
authors.initials: JC
authors.lastname: Jeong
authors.forename: Aravind
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Sabine
authors.initials: S
authors.lastname: Grüschow
authors.forename: Horacio
authors.initials: H
authors.lastname: Bach
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D009285:Naphthoquinones / Q000138:chemical synthesis; D011753:Pyrones / Q000138:chemical synthesis*; D048372:Streptomyces coelicolor / Q000201:enzymology*
chemical_list: D000214:Acyl Coenzyme A; D009285:Naphthoquinones; D011753:Pyrones; C041659:flaviolin; D008316:Malonyl Coenzyme A; D000217:Acyltransferases; C020141:flavanone synthetase