title: A comprehensive and engaging overview of the type III family of polyketide synthases.
abstract: Customizing biosynthesis of natural products to yield biologically active derivatives has captivated scientists in the field of biosynthetic research. To substantiate this goal, there are scores of obstacles to consider. To create novel metabolites by mutating amino acid residues in wild-type enzymes, a researcher must broaden the range of the enzymes substrate tolerance and increase its turnover rate during reaction catalysis. In the past decade, numerous gene clusters responsible for the biosynthesis of notable natural products have been identified from a variety of organisms. Several genes coding for type III polyketide synthases, particularly the chalcone synthase superfamily enzymes, were recently uncovered and expressed in E. coli. Furthermore, it was observed and reported how these recombinant enzymes are capable of producing essential metabolites in vitro. Three of the type III polyketide synthases, chalcone synthase, octaketide synthase and pentaketide chromone synthase, have been characterized and their active sites subjected to rational engineering for biosynthetic production of their analogs. Because they are encoded in a single open reading frame and are post-translationally small in size, type III polyketide synthases are ideal targets for protein engineering. The relative ease with which these genes are expressed makes molecular biological manipulation to obtain mutated enzymes more procurable, ameliorating analysis of its biosynthetic pathway. In summary, time devoted to modification of biosynthetic proteins and unravelling of the detailed reaction mechanisms involved in biosynthesis will be shortened, paving the way for a much wider scope for metabolic engineers in future. This review focuses on the use of chalcone synthase, octaketide synthase and pentaketide chromone synthase for rational biosynthetic engineering to generate molecular diversity and pursue innovative, biologically potent compounds.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California 1985 Zonal Ave PSC 718 Los Angeles, California 90033, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Alex P
authors.initials: AP
authors.lastname: Praseuth
authors.forename: Clay C C
authors.initials: CC
authors.lastname: Wang
mesh_terms: D048630:Polyketide Synthases / Q000378:metabolism*; D015202:Protein Engineering
chemical_list: D048630:Polyketide Synthases