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 1551-1559

Subject Categories

Cell Biology

Chemical Process Engineering

Energy Systems

DOI

10.1038/s42255-022-00654-1

PubMed

36302903

More information

Latest update

3/7/2024 9