Effect of metabolic regulators and aeration on isocitric acid synthesis by yarrowia lipolytica grown on ester-aldehyde fraction

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.