Reprogramming Yeast Metabolism from Alcoholic Fermentation to Lipogenesis
Journal article, 2018

Engineering microorganisms for production of fuels and chemicals often requires major re-programming of metabolism to ensure high flux toward the product of interest. This is challenging, as millions of years of evolution have resulted in establishment of tight regulation of metabolism for optimal growth in the organism's natural habitat. Here, we show through metabolic engineering that it is possible to alter the metabolism of Saccharomyces cerevisiae from traditional ethanol fermentation to a pure lipogenesis metabolism, resulting in high-level production of free fatty acids. Through metabolic engineering and process design, we altered subcellular metabolic trafficking, fine tuned NADPH and ATP supply, and decreased carbon flux to biomass, enabling production of 33.4 g/L extracellular free fatty acids. We further demonstrate that lipogenesis metabolism can replace ethanol fermentation by deletion of pyruvate decarboxylase enzymes followed by adaptive laboratory evolution. Genome sequencing of evolved strains showed that pyruvate kinase mutations were essential for this phenotype.

adaptive laboratory evolution

fatty acids

synthetic biology

metabolism

metabolic engineering

Crabtree effect

lipid

Author

Tao Yu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Yongjin Zhou

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Mingtao Huang

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Quanli Liu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Rui Pereira

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Florian David

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Cell

0092-8674 (ISSN) 1097-4172 (eISSN)

Vol. 174 6 1549-1572

Subject Categories

Chemical Process Engineering

Microbiology

Biocatalysis and Enzyme Technology

DOI

10.1016/j.cell.2018.07.013

PubMed

30100189

More information

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7/5/2024 1