Light-Driven Biosynthesis of myo-Inositol Directly From CO₂ in Synechocystis sp. PCC 6803

myo-inositol (MI) is an essential growth factor, nutritional source, and important precursor for many derivatives like D-chiro-inositol. In this study, attempts were made to achieve the "green biosynthesis" of MI in a model photosynthetic cyanobacterium Synechocystis sp. PCC 6803. First, several genes encoding myo-inositol-1-phosphate synthases and myo-inositol-1-monophosphatase, catalyzing the first or the second step of MI synthesis, were introduced, respectively, into Synechocystis. The results showed that the engineered strain carrying myo-inositol-1-phosphate synthase gene from Saccharomyces cerevisiae was able to produce MI at 0.97 mg L^-1. Second, the combined overexpression of genes related to the two catalyzing processes increased the production up to 1.42 mg L^-1. Third, to re-direct more cellular carbon flux into MI synthesis, an inducible small RNA regulatory tool, based on MicC-Hfq, was utilized to control the competing pathways of MI biosynthesis, resulting in MI production of ∼7.93 mg L^-1. Finally, by optimizing the cultivation condition via supplying bicarbonate to enhance carbon fixation, a final MI production up to 12.72 mg L^-1 was achieved, representing a ∼12-fold increase compared with the initial MI-producing strain. This study provides a light-driven green synthetic strategy for MI directly from CO₂ in cyanobacterial chassis and represents a renewable alternative that may deserve further optimization in the future.