Engineering of Escherichia coli for the biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from glucose.

The copolymer poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] has the potential to serve as a biodegradable tissue engineering material. However, the production of this kind of copolymer still suffers from high cost and uncertainty. We describe here the design of metabolic pathways to synthesize P(HB-co-HHx) directly from glucose using recombinant Escherichia coli. By combining the BktB-dependent condensation pathway with the inverted β-oxidation cycle pathway, we were able to synthesize a P(HB-co-HHx) copolymer with a 10 mol% HHx fraction in recombinant E. coli. After optimizing the host strain and employing thioesterase mutant strains, the engineered E. coli produced 12.9 wt% P(HB-co-HHx) with a 13.2 mol% 3HHx fraction.