Synthesis of poly(4HB-co-PhLA) and poly(3HB-co-4HB-co-PhLA) as sustainable hot-melt adhesives using engineered...

Conventional petroleum-based adhesives are non-biodegradable and raise environmental concerns. Polyhydroxyalkanoates (PHAs), bacterial polyesters synthesized from renewable carbon sources, are promising adhesive candidates due to biodegradability and structural diversity. Here, we report aromatic PHA copolymers, poly[4-hydroxybutyrate(4HB)-co-phenyllactate(PhLA)] and poly[3-hydroxybutyrate(3HB)-co-4HB-co-PhLA], exhibiting thermal stability and hot-melt adhesive (HMA) properties. Escherichia coli strains are engineered to produce these polymers from glucose and polymer biosynthesis is enhanced by optimizing heterologous expression, introducing additional CoA transferases and temporally regulating gene expression. We applied in silico simulations to systematically identify engineering targets that improve the synthesis of multiple monomers. The final engineered strains produce 10.2 g l^-1 of poly(32.7 mol% 4HB-co-PhLA) and 52.8 g l^-1 of poly(3HB-co-2.7 mol% 4HB-co-5.6 mol% PhLA). The resulting polymers demonstrate adhesive performance and reusability, expanding the available polymer property portfolio. Overall, we present a sustainable and expandable strategy for the microbial production of reusable, bio-based HMAs with tunable adhesive properties and practical application potential.