Recent advances in Chlamydomonas reinhardtii as a green factory for sustainable biofuels and bioproduct production.

This review highlights recent advances in engineering Chlamydomonas reinhardtii for the integrated production of biofuels and high-value bioproducts, emphasizing its potential in a circular bioeconomy. While these two areas are often studied separately, their combined consideration offers a more holistic view of sustainable resource utilization. As a versatile photosynthetic eukaryote, C. reinhardtii efficiently converts light energy and CO₂ into diverse bio-based compounds. It supports three main biofuel pathways: triacylglycerol accumulation under nutrient stress for biodiesel, fermentative ethanol production under dark anoxic conditions, and photobiological hydrogen evolution via hydrogenase under oxygen-limited conditions. Beyond biofuels, C. reinhardtii serves as a promising platform for producing high-value bioproducts, including recombinant proteins such as antibodies, vaccine antigens, antimicrobial peptides, and industrial enzymes, with minimal biosafety concerns. It can also be engineered to synthesize carotenoids, polysaccharides, and biodegradable polymers, expanding its applications in pharmaceutical, nutraceutical, and materials sectors. Its well-characterized genetic system, combined with advanced synthetic biology tools, enables precise metabolic engineering to enhance productivity and stability. Scalable cultivation in closed photobioreactors, integrated with CO₂ recycling and wastewater utilization, further supports environmental and economic sustainability. Despite significant progress, challenges remain in understanding carbon and redox allocation, chloroplast-lipid droplet interactions, and ensuring product consistency. Additional bottlenecks include limitations in scale-up, growth-productivity trade-offs, and costly downstream processing. Future efforts should focus on modular engineering, omics-guided optimization, and TEA/LCA-driven strategies to enable cost-effective, carbon-neutral biomanufacturing.