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

So Young Choi, Si Jae Park, Won Jun Kim, Jung Eun Yang, Hyuk Lee, Jihoon Shin, Sang Yup Lee

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

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.

Original languageEnglish
Pages (from-to)435-440
Number of pages6
JournalNature Biotechnology
Volume34
Issue number4
DOIs
StatePublished - 1 Apr 2016

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