One-step fermentative production of poly(lactate-co-glycolate) from carbohydrates in Escherichia coli

Nat Biotechnol. 2016 Apr;34(4):435-40. doi: 10.1038/nbt.3485. Epub 2016 Mar 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Fermentation / genetics*
  • Gene Knockout Techniques
  • Genes, Bacterial / genetics
  • Glucose / metabolism*
  • Lactic Acid / metabolism*
  • Metabolic Engineering / methods*
  • Metabolic Networks and Pathways / genetics
  • Polyglycolic Acid / metabolism*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Xylose / metabolism*

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Xylose
  • Glucose