Reprogramming Yeast Metabolism from Alcoholic Fermentation to Lipogenesis
Artikel i vetenskaplig tidskrift, 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.

fatty acids

lipid

adaptive laboratory evolution

metabolism

synthetic biology

Crabtree effect

metabolic engineering

Författare

Tao Yu

Chalmers, Biologi och bioteknik, Systembiologi

Yongjin Zhou

Chalmers, Biologi och bioteknik, Systembiologi

Mingtao Huang

Chalmers, Biologi och bioteknik, Systembiologi

Quanli Liu

Chalmers, Biologi och bioteknik, Systembiologi

Rui Pereira

Chalmers, Biologi och bioteknik, Systembiologi

Florian David

Chalmers, Biologi och bioteknik, Systembiologi

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Cell

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

Vol. 174 6 1549-1572

Ämneskategorier

Kemiska processer

Mikrobiologi

Biokatalys och enzymteknik

DOI

10.1016/j.cell.2018.07.013

PubMed

30100189

Mer information

Senast uppdaterat

2018-10-02