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

175 Scopus citations


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
Issue number4
StatePublished - 1 Apr 2016

Bibliographical note

Funding Information:
We thank S. Choi for the pTrc99s4 plasmid. This work was supported by the Technology Development Program to Solve Climate Changes (Systems Metabolic Engineering for Biorefineries) of the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation of Korea ((NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) to S.Y.C., W.J.K., J.E.Y., S.J.P. and S.Y.L.).

Publisher Copyright:
© 2016 Nature America, Inc. All rights reserved.


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