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

Zhihui Shi, Zhaoyu Xu, Weihe Rong, Hongbing Sun, Hongyi Zhou, Qianqian Yuan, Aixuan Xiao, Hongfei Ma, Tao Cai (), Guokun Wang () and Yanhe Ma ()
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Zhihui Shi: Chinese Academy of Sciences
Zhaoyu Xu: Chinese Academy of Sciences
Weihe Rong: Chinese Academy of Sciences
Hongbing Sun: Chinese Academy of Sciences
Hongyi Zhou: Chinese Academy of Sciences
Qianqian Yuan: Chinese Academy of Sciences
Aixuan Xiao: Chinese Academy of Sciences
Hongfei Ma: Chinese Academy of Sciences
Tao Cai: Chinese Academy of Sciences
Guokun Wang: Chinese Academy of Sciences
Yanhe Ma: Chinese Academy of Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-58067-z

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