Mitigating protocatechuic acid toxicity in Vibrio natriegens enables poly-3-hydroxybutyrate production from an aromatic carbon source

⁺. These strategies reduced PCA autoxidation and limited reactive oxygen species (ROS) toxicity. Adaptive laboratory evolution over ~ 1000 generations identified convergent mutations that reveal insights into the architecture of the oxidative stress response in V. natriegens, including catalytic enzymes such as a Dyp-type peroxidase, and multiple regulatory proteins including OxyR, MarR, RpoS, ToxS, and RseB. Further mutations implicate cell wall repair and protein quality control in the PCA stress response. Functionally, the adapted strains produced 2.5-fold more PHB in 80% of the time required by the parental strain. Overall, we demonstrate the potential and current limitations of V. natriegens for the sustainable upcycling of aromatic, waste-derived carbon into value-added bioproducts.