Metabolic engineering of Saccharomyces cerevisiae for overproduction of triacylglycerols
Artikel i vetenskaplig tidskrift, 2018

Triacylglycerols (TAGs) are valuable versatile compounds that can be used as metabolites for nutrition and health, as well as feedstocks for biofuel production. Although Saccharomyces cerevisiae is the favored microbial cell factory for industrial production of biochemicals, it does not produce large amounts of lipids and TAGs comprise only ~1% of its cell dry weight. Here, we engineered S. cerevisiae to reorient its metabolism for overproduction of TAGs, by regulating lipid droplet associated-proteins involved in TAG synthesis and hydrolysis. We implemented a push-and-pull strategy by overexpressing genes encoding a deregulated acetyl-CoA carboxylase, ACC1 S659A/S1157A (ACC1**), as well as the last two steps of TAG formation: phosphatidic phosphatase (PAH1) and diacylglycerol acyltransferase (DGA1), ultimately leading to 129 mg∙gCDW −1 of TAGs. Disruption of TAG lipase genes TGL3, TGL4, TGL5 and sterol acyltransferase gene ARE1 increased the TAG content to 218 mg∙gCDW −1 . Further disruption of the beta-oxidation by deletion of POX1, as well as glycerol-3-phosphate utilization through deletion of GUT2, did not affect TAGs levels. Finally, disruption of the peroxisomal fatty acyl-CoA transporter PXA1 led to accumulation of 254 mg∙gCDW −1 . The TAG levels achieved here are the highest titer reported in S. cerevisiae, reaching 27.4% of the maximum theoretical yield in minimal medium with 2% glucose. This work shows the potential of using an industrially established and robust yeast species for high level lipid production.

Författare

Raphael Ferreira

Chalmers, Biologi och bioteknik, Systembiologi

Paulo Teixeira

Chalmers, Biologi och bioteknik, Systembiologi

Michael Gossing

Chalmers, Biologi och bioteknik, Systembiologi

Florian David

Chalmers, Biologi och bioteknik, Systembiologi

Verena Siewers

Chalmers, Biologi och bioteknik, Systembiologi

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Metabolic Engineering Communications

2214-0301 (eISSN)

Vol. 6 22-27

Ämneskategorier

Växtbioteknologi

Biokatalys och enzymteknik

Annan industriell bioteknik

DOI

10.1016/j.meteno.2018.01.002