title: Energy- and carbon-efficient synthesis of functionalized small molecules in bacteria using non-decarboxylative Claisen condensation reactions.
abstract: Anabolic metabolism can produce an array of small molecules, but yields and productivities are low owing to carbon and energy inefficiencies and slow kinetics. Catabolic and fermentative pathways, on the other hand, are carbon and energy efficient but support only a limited product range. We used carbon- and energy-efficient non-decarboxylative Claisen condensation reactions and subsequent β-reduction reactions, which can accept a variety of functionalized primers and functionalized extender units and operate in an iterative manner, to synthesize functionalized small molecules. Using different ω- and ω-1-functionalized primers and α-functionalized extender units in combination with various termination pathways, we demonstrate the synthesis of 18 products from 10 classes, including ω-phenylalkanoic, α,ω-dicarboxylic, ω-hydroxy, ω-1-oxo, ω-1-methyl, 2-methyl, 2-methyl-2-enolic and 2,3-dihydroxy acids, β-hydroxy-ω-lactones, and ω-1-methyl alcohols.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, USA.
authors.forename: Seokjung
authors.identifier: 0000-0002-5699-2278
authors.initials: S
authors.lastname: Cheong
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Clomburg
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, USA.|Department of Bioengineering, Rice University, Houston, Texas, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Gonzalez
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001688:Biological Products / Q000302:isolation & purification / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D024861:Genetic Enhancement / Q000379:methods; D015202:Protein Engineering / Q000379:methods*
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products; D002244:Carbon