Biomanufacturing polyhydroxyalkanoates from CO2: A critical review of advances, challenges, and solutions for autotrophic and hybrid systems.

The bioconversion of carbon dioxide (CO2) into polyhydroxyalkanoates (PHAs) represents a transformative paradigm at the nexus of climate mitigation and sustainable manufacturing, offering a route to valorize a greenhouse gas (GHG) liability into high-value, biodegradable polymers. This critical review provides a systematic analysis of the technological landscape for CO2-to-PHA bioconversion, comparing the two dominant strategies: direct, single-organism autotrophic routes and modular, two-step hybrid systems that couple abiotic CO2 reduction with microbial fermentation. While direct autotrophic processes offer conceptual simplicity, they exhibit a wide performance gap: photoautotrophs are typically constrained by low volumetric productivities (<10 mg L-1 h-1) due to light limitation, whereas optimized chemoautotrophic systems (e.g., Cupriavidus necator) can achieve significantly higher rates of up to 1.55 g L-1 h-1. In contrast, two-step hybrid systems show promise for modularity by decoupling CO2 activation from biosynthesis. However, current integrated platforms generally demonstrate productivities in the milligram range (e.g., <25 mg L-1 h-1). Critical bottlenecks, specifically inefficient gas-liquid mass transfer (low kLa), catalyst instability (<100 h lifetime), and the high energy penalty of downstream separation, persist across all platforms. Currently keeping production costs ($3-8/kg) well above the economic threshold. The path forward requires a strategic roadmap focused on three pillars: dynamic metabolic control via synthetic biology, process intensification using advanced reactor engineering, and holistic system integration. The successful convergence of these disciplines, supported by robust techno-economic frameworks and life-cycle assessments, is critical to transforming CO2-to-PHA bioconversion from a promising concept into a cornerstone technology for the circular bioeconomy.