title: Novel applications of plant polyketide synthases.
abstract: The structurally and mechanistically simple type III polyketide synthases (PKSs) catalyze iterative condensations of CoA thioesters to produce a variety of polyketide scaffolds with remarkably diverse structures and biological activities. By exploiting the enzymes, we combined precursor-directed biosynthesis with nitrogen-containing substrates and structure-based enzyme engineering and generated unnatural, novel polyketide-alkaloid scaffolds with promising biological activities. The nucleophilic nitrogen atom and the engineered enzymes thus facilitated the formation of additional CC and CN bonds during the enzymatic transformations. The methodology will contribute to the further production of chemically and structurally divergent, unnatural natural products, as well as the rational design of novel biocatalysts with unprecedented catalytic functions.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D055162:Biocatalysis; D010944:Plants / Q000201:enzymology*; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism; D011760:Pyrrolidinones / Q000737:chemistry / Q000378:metabolism
chemical_list: D061065:Polyketides; D011760:Pyrrolidinones; C009435:tetramic acid; D048630:Polyketide Synthases