Abstract:Protein is a crucial nutrient for human beings, and its stable and high-quality supply is the key to improving people’s living standards and ensuring national food security. Currently, due to the high dependence on imported protein, there is a pressing need for new technologies to produce high-quality protein through non-food approaches. A promising candidate is the green microalga Chlamydomonas reinhardtii (C. reinhardtii), which has shown potential for producing dietary protein through fermentation on acetate. However, this method ignores the advantage of photosynthesis in green bio-manufactory. Here, the author demonstrated the feasibility of utilizing formate, one of the products of CO2 reduction driven by clean energy, to enhance the photosynthetic production of C. reinhardtii. To eliminate the serious inhibition of HCOO- on photosynthetic activity, the author employed adaptive lab evolution with the guide by chlorophyll fluorescence dynamic parameters and obtained a domesticated stain capable of growing under as high as 150 mmol/L HCOO-.With the addition of 50~150 mmol/L HCOO-, the strain maintained stable the maximum quantum yield of PSⅡ (Fv/Fm), preserved a consistent fatty acid profile, and achieved a growth rate similar to acetate addition in batch cultures. Moreover, the protein content of biomass obtained with HCOO- was 30%~35%, comparable to or even higher than that of commercial fermentation on acetate. This work provides a novel green approach for non-food sourced protein production through artificial-natural hybrid photosynthesis. Furthermore, the high HCOO--tolerant strain serves as an excellent model to investigate the regulation of photosynthesis.