title: One-step fermentative production of poly(lactate-co-glycolate) from carbohydrates in Escherichia coli.
abstract: Poly(lactate-co-glycolate) (PLGA) is a widely used biodegradable and biocompatible synthetic polymer. Here we report one-step fermentative production of PLGA in engineered Escherichia coli harboring an evolved polyhydroxyalkanoate (PHA) synthase that polymerizes D-lactyl-CoA and glycolyl-CoA into PLGA. Introduction of the Dahms pathway enables production of glycolate from xylose. Deletion of ptsG enables simultaneous utilization of glucose and xylose. An evolved propionyl-CoA transferase converts D-lactate and glycolate to D-lactyl-CoA and glycolyl-CoA, respectively. Deletion of adhE, frdB, pflB and poxB prevents by-product formation. We also demonstrate modulation of the monomer fractions in PLGA by overexpressing ldhA and deleting dld to increase the proportion of D-lactate or by deleting aceB, glcB, glcD, glcE, glcF and glcG to increase the proportion of glycolate. Incorporation of 2-hydroxybutyrate is prevented by deleting ilvA or feeding strains with L-isoleucine. The utility of our approach for generating diverse forms of PLGA is shown by the production of copolymers containing 3-hydroxybutyrate, 4-hydroxybutyrate or 2-hydroxyisovalerate.
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, and Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Environmental Engineering and Energy, Myongji University, Yongin, Gyeonggido, Republic of Korea.
authors.forename: Si Jae
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, and Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, and Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Yang
authors.affiliation: Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Lee
authors.affiliation: Center for Bio-based Chemistry, Green Chemistry and Engineering Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, and Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Sang Yup
authors.identifier: http://orcid.org/0000-0003-0599-3091
authors.initials: SY
authors.lastname: Lee
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005285:Fermentation / Q000235:genetics*; D055786:Gene Knockout Techniques; D005798:Genes, Bacterial / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D011100:Polyglycolic Acid / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014994:Xylose / Q000378:metabolism*
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014994:Xylose; D005947:Glucose