Cultivation in a Natural Microbial Community Enhances the Industrial Performance of a Genetically Engineered...

Large-scale production of polyhydroxybutyrate (PHB), a biodegradable bioplastic, using genetically engineered cyanobacteria offers a sustainable alternative to petrochemical-derived plastics. However, monoculture-based phototrophic systems face major limitations, such as poor resilience in large-scale reactors, hindering industrial upscaling. To address these challenges, we replaced the native cyanobacterium of a natural microbial consortium with a genetically engineered Synechocystis strain optimised for PHB production, establishing what we define a hybrid photosynthetic microbiome. This new community preserved the ecological structure and stability of the original microbiome while gaining synthetic production capacity. Compared to the axenic strain, the hybrid system exhibited enhanced robustness under abiotic stress, including light and temperature fluctuations, and improved tolerance to operational instability. These features made it suitable for upscaling and application in non-sterile environments. The hybrid microbiome sustained PHB production in scaled photobioreactors, reaching up to 32% PHB per cell dry weight (CDW) equal to ~230 mg L^-1 under fully photoautotrophic conditions. Production was also achieved under dark conditions with acetate supplementation, highlighting the system's metabolic flexibility. This work demonstrates the successful integration of an engineered phototroph into a stable native microbiome, positioning hybrid communities as powerful platform for industrial biotechnology.