Reprogramming yeast metabolism for customized starch-rich micro-grain through low-carbon microbial manufacturing

Starch is a primary food ingredient and industrial feedstock. Low-carbon microbial manufacturing offers a carbon-neutral/negative arable land-independent strategy for starch production. Here, we reconfigure the oleaginous yeast as a starch-rich micro-grain producer by rewiring the starch biosynthesis and gluconeogenesis pathways and regulating cell morphology. With the CO2 electro-synthesized acetate as the substrate, the strain accumulates starch 47.18% of dry cell weight. The optimized system renders spatial-temporal starch productivity (243.7 g/m2/d) approximately 50-fold higher than crop cultivation and volumetric productivity (160.83 mg/L/h) over other microbial systems by an order of magnitude. We demonstrate tunable starch composition and starch-protein ratios via strain and process engineering. The engineered artificial strains adopt a cellular resources reallocation strategy to ensure high-level starch production in micro-grain and could facilitate a highly efficient straw/cellulose-to-starch conversion. This work elucidates starch biosynthesis machinery and establishes a superior-to-nature platform for customizable starch synthesis, advancing low-carbon nutritional manufacturing. Starch is a primary food ingredient and bulk industrial feedstock. Here, the authors employ metabolic engineering and cell morphology control strategies to engineer oleaginous yeast Yarrowia lipolytica for starch biosynthesis using acetate as sole carbon source.