Engineering Access to Stereoirregular Polymer Microstructures Enables Improved Processability of Microbial...

Poly(3-hydroxybutyrate) (PHB) is a biocompatible and biodegradable polyhydroxyalkanoate, but its highly regular stereomicrostructure causes high crystallinity and poor processability. Here, we demonstrate that stereoirregular PHB can be produced microbially, challenging the view that strict PHA synthase stereospecificity makes such structures inaccessible. In a proof-of-concept study, we produced stereoirregular PHB containing 6.84% ± 0.04% (S)-3-hydroxybutyrate, with an m-dyad fraction of 11.8% ± 0.7%. Compared with conventional PHB, the stereoirregular material exhibited a reduced melting temperature, from 179.3 °C ± 0.7 to 154.3 °C ± 1.1 °C, and decreased molar-mass decomposition during processing. These results demonstrate that microbial synthesis can access stereochemically diverse PHB. Importantly, they show that biologically produced polymers can exhibit the improved processability and recyclability previously associated with chemically synthesized analogues. These findings overturn a long-standing assumption in PHB biosynthesis and provide a basis for biologically tuning polymer microstructure and performance through microbial engineering.