Microbial synthesis of lactate-containing polyesters

Microbially synthesized polyesters are promising sustainable alternatives to petroleum-based plastics because they are biodegradable and derived from renewable resources. Incorporating lactate (LA) is particularly attractive due to the distinct material properties it confers. However, efficient lactate incorporation is constrained by the substrate specificity of PHA synthase, which naturally prefers 3HB-CoA over LA-CoA. Although engineered PHA synthase variants can incorporate lactate, their low catalytic efficiency yields only minor lactate fractions, making the absence of an efficient lactate-polymerizing synthase a major bottleneck for producing lactate-based polyesters.
To advance biosynthesis of tailored lactate-containing polyesters and enable microbial platforms to produce materials comparable to chemically synthesized polymers, this project developed genetic constructs for biosynthesis of P(3HB-co-LA) in E. coli and V. natriegens. Copolymer production was confirmed by NMR and GC. To improve yield and control lactate fraction, we systematically explored: (1) engineered PHA synthases with enhanced lactate polymerization; (2) alternative host strains; (3) supplementation with exogenous lactate; and (4) plasmids with inducible copy number to tune gene expression. These integrated strategies increased both copolymer yield and monomer composition, achieving lactate fractions up to ~14% and a polymer titer of 6.6 g·L⁻¹. Previous reports have reached higher titers 8-10 g·L⁻¹ and lactate fractions up to 64%, often under 5 L fermenter conditions. In our flask cultures, polymer titers were consistently below 1 g·L⁻¹ with lactate fractions of 10–20%. Compared at similar lab scale, our yield shows marked improvement, although lactate incorporation remains comparatively limited.