title: Engineering Escherichia coli for Conversion of Glucose to Medium-Chain ω-Hydroxy Fatty Acids and α,ω-Dicarboxylic Acids.
abstract: In search of sustainable approaches to plastics production, many efforts have been made to engineer microbial conversions of renewable feedstock to short-chain (C2-C8) bifunctional polymer precursors (e.g., succinic acid, cadaverine, 1,4-butanediol). Less attention has been given to medium-chain (C12-C14) monomers such as ω-hydroxy fatty acids (ω-OHFAs) and α,ω-dicarboxylic acids (α,ω-DCAs), which are precursors to high performance polyesters and polyamides. Here we engineer a complete microbial conversion of glucose to C12 and C14 ω-OHFAs and α,ω-DCAs, with precise control of product chain length. Using an expanded bioinformatics approach, we screen a wide range of enzymes across phyla to identify combinations that yield complete conversion of intermediates to product α,ω-DCAs. Finally, through optimization of culture conditions, we enhance production titer of C12 α,ω-DCA to nearly 600 mg/L. Our results indicate potential for this microbial factory to enable commercially relevant, renewable production of C12 α,ω-DCA-a valuable precursor to the high-performance plastic, nylon-6,12.
authors.affiliation: Department of Energy, Environmental, and Chemical Engineering, ‡Division of Biological & Biomedical Sciences, §Institute of Materials Science & Engineering, Washington University in Saint Louis , St. Louis, Missouri 63130, United States.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Bowen
authors.affiliation: Department of Energy, Environmental, and Chemical Engineering, ‡Division of Biological & Biomedical Sciences, §Institute of Materials Science & Engineering, Washington University in Saint Louis , St. Louis, Missouri 63130, United States.
authors.forename: Jeff
authors.initials: J
authors.lastname: Bonin
authors.affiliation: Department of Energy, Environmental, and Chemical Engineering, ‡Division of Biological & Biomedical Sciences, §Institute of Materials Science & Engineering, Washington University in Saint Louis , St. Louis, Missouri 63130, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Kogler
authors.affiliation: Department of Energy, Environmental, and Chemical Engineering, ‡Division of Biological & Biomedical Sciences, §Institute of Materials Science & Engineering, Washington University in Saint Louis , St. Louis, Missouri 63130, United States.
authors.forename: Carlos
authors.initials: C
authors.lastname: Barba-Ostria
authors.affiliation: Department of Energy, Environmental, and Chemical Engineering, ‡Division of Biological & Biomedical Sciences, §Institute of Materials Science & Engineering, Washington University in Saint Louis , St. Louis, Missouri 63130, United States.
authors.forename: Fuzhong
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D061249:Batch Cell Culture Techniques; D003998:Dicarboxylic Acids / Q000032:analysis / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D005818:Genetic Engineering; D005947:Glucose / Q000378:metabolism*; D010084:Oxidation-Reduction; D010957:Plasmids / Q000235:genetics / Q000378:metabolism
chemical_list: D003998:Dicarboxylic Acids; D005227:Fatty Acids; D000426:Alcohol Dehydrogenase; D005947:Glucose
keywords: alcohol dehydrogenase; aldehyde dehydrogenase; biobased plastics; medium-chain α,ω-dicarboxylic acids; medium-chain ω-hydroxy fatty acids; nylon-6,12