Metabolic reconfiguration enables synthetic reductive metabolism in yeast

Yu, Tao,1988Chalmers tekniska högskola,Chalmers University of Technology,Shenzhen Institute of Advanced Technology,Danmarks Tekniske Universitet,Technical University of Denmark,Novo Nordisk Fonden,Novo Nordisk Foundation (author)

Cell proliferation requires the integration of catabolic processes to provide energy, redox power and biosynthetic precursors. Here we show how the combination of rational design, metabolic rewiring and recombinant expression enables the establishment of a decarboxylation cycle in the yeast cytoplasm. This metabolic cycle can support growth by supplying energy and increased provision of NADPH or NADH in the cytosol, which can support the production of highly reduced chemicals such as glycerol, succinate and free fatty acids. With this approach, free fatty acid yield reached 40% of theoretical yield, which is the highest yield reported for Saccharomyces cerevisiae to our knowledge. This study reports the implementation of a synthetic decarboxylation cycle in the yeast cytosol, and its application in achieving high yields of valuable chemicals in cell factories. Our study also shows that, despite extensive regulation of catabolism in yeast, it is possible to rewire the energy metabolism, illustrating the power of biodesign.

Liu, Quanli,1988Novo Nordisk Fonden,Novo Nordisk Foundation,Danmarks Tekniske Universitet,Technical University of Denmark,Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)quanli (author)
Wang, XiangShenzhen Institute of Advanced Technology (author)
Liu, XiangjianShenzhen Institute of Advanced Technology (author)
Chen, Yun,1978Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology,Danmarks Tekniske Universitet,Technical University of Denmark(Swepub:cth)yunc (author)
Nielsen, Jens B,1962Novo Nordisk Fonden,Novo Nordisk Foundation,Chalmers tekniska högskola,Chalmers University of Technology,Danmarks Tekniske Universitet,Technical University of Denmark,BioInnovation Institute (BII)(Swepub:cth)nielsenj (author)
Chalmers tekniska högskolaShenzhen Institute of Advanced Technology (creator_code:org_t)

In:Nature Metabolism: Springer Science and Business Media LLC4:11, s. 1551-15592522-5812

By the author/editor: Yu, Tao, 1988; Liu, Quanli, 198 ...; Wang, Xiang; Liu, Xiangjian; Chen, Yun, 1978; Nielsen, Jens B, ...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

ENGINEERING AND TECHNOLOGY: ENGINEERING AND ...; and Chemical Enginee ...; and Chemical Process ...

ENGINEERING AND TECHNOLOGY: ENGINEERING AND ...; and Environmental En ...; and Energy Systems

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