Metabolic reconfiguration enables synthetic reductive metabolism in yeast
Journal article, 2022
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.
Author
Tao Yu
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Shenzhen Institute of Advanced Technology
Technical University of Denmark (DTU)
Novo Nordisk Foundation
Quanli Liu
Novo Nordisk Foundation
Technical University of Denmark (DTU)
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Xiang Wang
Shenzhen Institute of Advanced Technology
Xiangjian Liu
Shenzhen Institute of Advanced Technology
Yun Chen
Novo Nordisk Foundation
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Technical University of Denmark (DTU)
Jens B Nielsen
Novo Nordisk Foundation
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Technical University of Denmark (DTU)
BioInnovation Institute
Nature Metabolism
25225812 (eISSN)
Vol. 4 11 1551-1559Subject Categories
Cell Biology
Chemical Process Engineering
Energy Systems
DOI
10.1038/s42255-022-00654-1
PubMed
36302903