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One-step fermentative production of poly(lactate-co-glycolate) from carbohydrates in Escherichia coli
- One-step fermentative production of poly(lactate-co-glycolate) from carbohydrates in Escherichia coli
- Choi, So Young; Park, Si Jae; Kim, Won Jun; Yang, Jung Eun; Lee, Hyuk; Shin, Jihoon; Lee, Sang Yup
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- NATURE BIOTECHNOLOGY
- NATURE BIOTECHNOLOGY vol. 34, no. 4, pp. 435 - +
- NATURE PUBLISHING GROUP
- SCIE; SCOPUS
- Document Type
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- 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.
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