Abstract
Isocitric acid (ICA) has found wide application in medicine as a promising compound with powerful antioxidant activity to combat oxidative stress. In the known microbiological processes of ICA production by non-conventional yeast Yarrowia lipolytica, the pure carbon sources are commonly used. ICA can be also synthetized by Y. lipolytica from ester-aldehyde fraction (EAF)-waste of the ethanol production process. A highly effective method of ICA production from EAF based on regulation of key enzymes (aconitate hydratase and isocitrate lyase) by metabolic regulators (iron and itaconic acid) and aeration was developed. It is recommended to cultivate Y. lipolytica VKM Y-2373 under nitrogen deficiency conditions, a high aeration (60% of air saturation), an addition of 15 mM itaconic acid, and 2.4 mg/L iron. Under optimal conditions, Y. lipolytica VKM Y-2373 produced 83 g/L ICA with isocitrate to citrate ratio of 4.1:1 and mass yield of 1.1 g/g. The putative mechanism of ICA overproduction from EAF by Y. lipolytica was suggested.
Highlights
In recent decades, interest in the study of non-conventional yeast Yarrowia lipolytica has increased due to their difference from the well-studied yeast Saccharomyces cerevisiae in terms of their phylogenetic evolution, physiology, genetics, and their use in biotechnology [1,2]
The effect of itaconic acid was studied in the range of 10–80 mM, and as a control, The effect of itaconic acid was studied in thethe range of 10–80 and acid
The novelty of the work lies in the study of the regulation of the biosynthesis of isocitric acid (ICA) from a poorly studied substrate, ether-aldehyde fraction (EAF) in the yeast Y. lipolytica
Summary
Interest in the study of non-conventional yeast Yarrowia lipolytica has increased due to their difference from the well-studied yeast Saccharomyces cerevisiae in terms of their phylogenetic evolution, physiology, genetics, and their use in biotechnology [1,2]. Y. lipolytica differs from facultative anaerobe of S. cerevisiae in that it is an obligate aerobe [3], that is, its metabolism depends entirely on the functioning of mitochondria. Y. lipolytica is separated from the cultivation medium, does not pollute the air with spores [1,2,3]. The synthesized metabolites of Y. lipolytica are admitted as safe [4]. Wild and recombinant strains of Y. lipolytica are considered as microbial factories to produce valuable metabolites in industrially significant quantities, such as lipids [5,6], polyols (erythritol and mannitol) [7,8,9,10], and citric acid (CA) [5,9,10,11,12]
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