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Fine-tuning mitochondrial activity in Yarrowia lipolytica for citrate overproduction

Jorgelindo da Veiga Moreira, Mario Jolicoeur, Laurent Schwartz and Sabine Peres

Article (2021)

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Abstract

Yarrowia lipolytica is a non-conventional yeast with promising industrial potentials for lipids and citrate production. It is also widely used for studying mitochondrial respiration due to a respiratory chain like those of mammalian cells. In this study we used a genome-scale model (GEM) of Y. lipolytica metabolism and performed a dynamic Flux Balance Analysis (dFBA) algorithm to analyze and identify metabolic levers associated with citrate optimization. Analysis of fluxes at stationary growth phase showed that carbon flux derived from glucose is rewired to citric acid production and lipid accumulation, whereas the oxidative phosphorylation (OxPhos) shifted to the alternative respiration mode through alternative oxidase (AOX) protein. Simulations of optimized citrate secretion flux resulted in a pronounced lipid oxidation along with reactive oxygen species (ROS) generation and AOX flux inhibition. Then, we experimentally challenged AOX inhibition by adding n-Propyl Gallate (nPG), a specific AOX inhibitor, on Y. lipolytica batch cultures at stationary phase. Our results showed a twofold overproduction of citrate (20.5 g/L) when nPG is added compared to 10.9 g/L under control condition (no nPG addition). These results suggest that ROS management, especially through AOX activity, has a pivotal role on citrate/lipid flux balance in Y. lipolytica. All taken together, we thus provide for the first time, a key for the understanding of a predominant metabolic mechanism favoring citrate overproduction in Y. lipolytica at the expense of lipids accumulation.

Uncontrolled Keywords

Dynamical systems ; Industrial microbiology

Subjects: 1800 Chemical engineering > 1800 Chemical engineering
1800 Chemical engineering > 1802 Biochemical engineering
Department: Department of Chemical Engineering
PolyPublie URL: https://publications.polymtl.ca/9292/
Journal Title: Scientific Reports (vol. 11, no. 1)
Publisher: Springer Nature
DOI: 10.1038/s41598-020-79577-4
Official URL: https://doi.org/10.1038/s41598-020-79577-4
Date Deposited: 27 Feb 2023 14:02
Last Modified: 27 Feb 2024 11:28
Cite in APA 7: da Veiga Moreira, J., Jolicoeur, M., Schwartz, L., & Peres, S. (2021). Fine-tuning mitochondrial activity in Yarrowia lipolytica for citrate overproduction. Scientific Reports, 11(1), 878 (11 pages). https://doi.org/10.1038/s41598-020-79577-4

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