Abolishing storage lipids induces protein misfolding and stress responses in Yarrowia lipolytica
Journal article, 2023

Yarrowia lipolytica naturally saves excess carbon as storage lipids. Engineering efforts allow redirecting the high precursor flux required for lipid synthesis toward added-value chemicals such as polyketides, flavonoids, and terpenoids. To redirect precursor flux from storage lipids to other products, four genes involved in triacylglycerol and sterol ester synthesis (DGA1, DGA2, LRO1, and ARE1) can be deleted. To elucidate the effect of the deletions on cell physiology and regulation, we performed chemostat cultivations under carbon and nitrogen limitations, followed by transcriptome analysis. We found that storage lipid-free cells show an enrichment of the unfolded protein response, and several biological processes related to protein refolding and degradation are enriched. Additionally, storage lipid-free cells show an altered lipid class distribution with an abundance of potentially cytotoxic free fatty acids under nitrogen limitation. Our findings not only highlight the importance of lipid metabolism on cell physiology and proteostasis, but can also aid the development of improved chassy strains of Y. lipolytica for commodity chemical production.


Lipid classes

Fatty acid toxicity

Fat free Yarrowia lipolytica

Q4 strain


Simone Zaghen

Chalmers, Life Sciences, Systems and Synthetic Biology

Oliver Konzock

Chalmers, Life Sciences, Systems and Synthetic Biology

Jing Fu

Chalmers, Life Sciences, Systems and Synthetic Biology

Eduard Kerkhoven

Chalmers, Life Sciences, Systems and Synthetic Biology

Novo Nordisk Foundation

Journal of Industrial Microbiology and Biotechnology

1367-5435 (ISSN) 1476-5535 (eISSN)

Vol. 50 1 kuad031

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Subject Categories

Pharmacology and Toxicology


Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)





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