Metabolic reconfiguration enables synthetic reductive metabolism in yeast

Tao Yu*, Quanli Liu, Xiang Wang, Xiangjian Liu, Yun Chen, Jens Nielsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.

Original languageEnglish
JournalNature Metabolism
Issue number11
Pages (from-to)1551-1559
Publication statusPublished - 2022


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