Abstract
Within this work, the microbial synthesis of (2R,3S)-isocitric acid (ICA), a metabolite of the nonconventional yeast Yarrowia lipolytica, from biodiesel waste, has been studied. The selected strain Y. lipolytica VKM Y-2373 synthesized ICA with citric acid (CA) as a byproduct. This process can be regulated by changing cultivation conditions. The maximal production of ICA with the minimal formation of the byproduct was provided by the use of a concentration of (NH4)2SO4 (6 g/L); the addition of biodiesel waste to cultivation medium in 20–60 g/L portions; maintaining the pH of the cultivation medium at 6, and degree of aeration between 25% and 60% of saturation. Itaconic acid at a concentration of 15 mM favorably influenced the production of ICA by the selected strain. The optimization of cultivation conditions allowed us to increase the concentration of ICA in the culture liquid from 58.32 to 90.2 g/L, the product yield (Y) by 40%, and the ICA/CA ratio from 1.1:1 to 3:1. Research on laboratory animals indicated that ICA counteracted the negative effect of ammonium molybdate (10−5 M) and lead diacetate (10−7 M) on the learning and spatial memory of rats, including those exposed to emotional stress.
Highlights
The interest in isocitric acid (ICA) is associated with its potential efficiency in the treatment of Parkinson’s disease, Fe-deficiency anemia, and metabolic myopathies associated with a shortage of succinate dehydrogenase and aconitate hydratase, as well as the mutation of the gene of NADP-dependent isocitrate dehydrogenase 1 (IDH1) as one possible reason for the emergence of neoplasms [1,2,3,4,5,6]
Taking into account the above information, the results of this study suggest that the spatial transformation of the conditioned active avoidance response (CAAR) causes oxidative stress in the tested animals and that the observed beneficial effect of ICA is explained by its antioxidant activity
The production of ICA by the wild strain Y. lipolytica VKM Y-2373 is maximum when the cultivation medium contains 6 g/L of (NH4)2SO4 as the nitrogen source; from 40 to 80 g/L of biodiesel waste as the source of carbon and energy; 15 mM of itaconic acid as the inhibitor of isocitrate lyase; and when the pH of the medium during cultivation is maintained at a level of 6.0–6.5
Summary
The interest in isocitric acid (ICA) is associated with its potential efficiency in the treatment of Parkinson’s disease, Fe-deficiency anemia, and metabolic myopathies associated with a shortage of succinate dehydrogenase and aconitate hydratase, as well as the mutation of the gene of NADP-dependent isocitrate dehydrogenase 1 (IDH1) as one possible reason for the emergence of neoplasms [1,2,3,4,5,6]. In experiments with oxidative stress induced by the action of hydrogen peroxide and ecotoxic heavy metals (Cu, Pb, Zn, Cd) on the Paramecium caudatum infusoria cells, the monopotassium salt of ICA was found to be a more efficient antioxidant than ascorbic acid [7]. ICA monopotassium salt mitigates the neurotoxic effect of lead and molybdenum salts, as is evident from its beneficial effect on the learning and memory inhibition in rats intoxicated with these heavy metal salts [8]. ICA is commonly produced by chemical synthesis with the formation of a mixture of stereoisomers extremely persistent for separation. The naturally occurring stereoisomer (2R,3S)-ICA produced by Sigma (USA) is isolated from the juice of the specially cultivated plant Sedum spectabile. There is increasing interest in the production of ICA by microbiological methods, because the end product predominantly contains the natural ICA isomer and has a high biological activity [1,2,3,4,5,6]
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