title: Insights into polyketide biosynthesis gained from repurposing antibiotic-producing polyketide synthases to produce fuels and chemicals.
abstract: Complex polyketides comprise a large number of natural products that have broad application in medicine and agriculture. They are produced in bacteria and fungi from enzyme complexes named type I polyketide synthases (PKSs) that are composed of multifunctional polypeptides containing discrete enzymatic domains organized into modules. The modular nature of PKSs has enabled a multitude of efforts to engineer the PKS genes to produce novel polyketides with enhanced or new properties. We have repurposed PKSs, employing up to three modules to produce a number of short-chain molecules that could have applications as fuels or industrial chemicals. Examining the enzymatic functions in vitro of these repurposed PKSs, we have uncovered a number of expanded substrate specificities and requirements of various PKS domains not previously reported and determined an unexpected difference in the order of enzymatic reactions within a module. In addition, we were able to efficiently change the stereochemistry of side chains in selected PKS products.
authors.affiliation: QB3 Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuzawa
authors.affiliation: QB3 Institute, University of California, Berkeley, CA 94720, USA.|Joint BioEnergy Institute, Emeryville, CA 94608, USA.|Department of Bioengineering, University of California, Berkeley, CA 94720, USA.|Synthetic Biology Research Center, Emeryville, CA 94608, USA.|Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.|Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
authors.affiliation: QB3 Institute, University of California, Berkeley, CA 94720, USA.|Synthetic Biology Research Center, Emeryville, CA 94608, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Katz
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D056804:Biofuels; D020134:Catalytic Domain; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism*; D015202:Protein Engineering; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D056804:Biofuels; D061065:Polyketides; D048630:Polyketide Synthases