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Engineered Corynebacterium glutamicum as an endotoxin-free platform strain for lactate-based polyester production

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Abstract

The first biosynthetic system for lactate (LA)-based polyesters was previously created in recombinant Escherichia coli (Taguchi et al. 2008). Here, we have begun efforts to upgrade the prototype polymer production system to a practical stage by using metabolically engineered Gram-positive bacterium Corynebacterium glutamicum as an endotoxin-free platform. We designed metabolic pathways in C. glutamicum to generate monomer substrates, lactyl-CoA (LA-CoA), and 3-hydroxybutyryl-CoA (3HB-CoA), for the copolymerization catalyzed by the LA-polymerizing enzyme (LPE). LA-CoA was synthesized by D-lactate dehydrogenase and propionyl-CoA transferase, while 3HB-CoA was supplied by β-ketothiolase (PhaA) and NADPH-dependent acetoacetyl-CoA reductase (PhaB). The functional expression of these enzymes led to a production of P(LA-co-3HB) with high LA fractions (96.8 mol%). The omission of PhaA and PhaB from this pathway led to a further increase in LA fraction up to 99.3 mol%. The newly engineered C. glutamicum potentially serves as a food-grade and biomedically applicable platform for the production of poly(lactic acid)-like polyester.

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Acknowledgments

We thank Dr. Jens Plassmeier for helpful discussions. The work described here was partially supported by a Grant-in-Aid for Scientific Research of Japan (no. 23310059) (to S.T.), and the Global COE Program (project no. B01: Catalysis as the Basis for Innovation in Materials Science) (to Y.S.), all from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Correspondence to Seiichi Taguchi.

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Song, Y., Matsumoto, K., Yamada, M. et al. Engineered Corynebacterium glutamicum as an endotoxin-free platform strain for lactate-based polyester production. Appl Microbiol Biotechnol 93, 1917–1925 (2012). https://doi.org/10.1007/s00253-011-3718-0

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