title: Engineering of plant type III polyketide synthases.
abstract: Members of the chalcone synthase superfamily of type III polyketide synthases (PKSs) catalyze iterative condensations of CoA thioesters to produce a variety of polyketide scaffolds with remarkable structural diversity and biological activities. The homodimeric type III PKSs share a common three-dimensional overall fold with a conserved Cys-His-Asn catalytic triad; notably, only a slight modification of the active site dramatically expands the catalytic repertoire of the enzymes. In addition, the enzymes exhibit extremely promiscuous substrate specificities, and accept a variety of nonphysiological substrates, making the type III PKSs an excellent platform for the further production of unnatural, novel polyketide scaffolds with promising biological activities. This chapter summarizes recent advances in the engineering of plant type III PKS enzymes in our laboratories, using approaches combining structure-based enzyme engineering and precursor-directed biosynthesis with rationally designed substrate analogs.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Wakimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000504:Aloe / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D002074:Butanones / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003653:Decarboxylation; D008958:Models, Molecular; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D011760:Pyrrolidinones / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D002074:Butanones; D010940:Plant Proteins; D061065:Polyketides; D011760:Pyrrolidinones; C009435:tetramic acid; C025383:benzylideneacetone; D000217:Acyltransferases; C020141:flavanone synthetase