Effects of overexpression of STB5 in Saccharomyces cerevisiae on fatty acid biosynthesis, physiology and transcriptome
Journal article, 2019

Microbial conversion of biomass to fatty acids (FA) and products derived thereof is an attractive alternative to the traditional oleochemical production route from animal and plant lipids. This study examined if NADPH-costly FA biosynthesis could be enhanced by overexpressing the transcription factor Stb5 in Saccharomyces cerevisiae. Stb5 activates expression of multiple genes encoding enzymes within the pentose phosphate pathway (PPP) and other NADPH-producing reactions. Overexpression of STB5 led to a decreased growth rate and an increased free fatty acid (FFA) production during growth on glucose. The improved FFA synthetic ability in the glucose phase was shown to be independent of flux through the oxidative PPP. RNAseq analysis revealed that STB5 overexpression had wide-ranging effects on the transcriptome in the batch phase, and appeared to cause a counterintuitive phenotype with reduced flux through the oxidative PPP. During glucose limitation, when an increased NADPH supply is likely less harmful, an overall induction of the proposed target genes of Stb5 (eg. GND1/2, TAL1, ALD6, YEF1) was observed. Taken together, the strategy of utilizing STB5 overexpression to increase NADPH supply for reductive biosynthesis is suggested to have potential in strains engineered to have strong ability to consume excess NADPH, alleviating a potential redox imbalance.

metabolic engineering

transcription factor

STB5

Saccharomyces cerevisiae

fatty acids

NADPH

Author

Alexandra Linda Bergman

Novo Nordisk Foundation

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Dóra Vitay

Student at Chalmers

John Hellgren

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Novo Nordisk Foundation

Yun Chen

Novo Nordisk Foundation

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Novo Nordisk Foundation

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Technical University of Denmark (DTU)

Verena Siewers

Novo Nordisk Foundation

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

FEMS Yeast Research

1567-1356 (ISSN) 1567-1364 (eISSN)

Vol. 19 3 foz027

Subject Categories

Microbiology

Plant Biotechnology

Biocatalysis and Enzyme Technology

DOI

10.1093/femsyr/foz027

PubMed

30924859

More information

Latest update

5/26/2023