Abstract

There is ever increasing evidence that isocitric acid can be used as a promising compound with powerful antioxidant activity to combat oxidative stress. This work demonstrates the possibility of using waste product from the alcohol industry (so-called ester-aldehyde fraction) for production of isocitric acid by yeasts. The potential producer of isocitric acid from this fraction, Yarrowia lipolytica VKM Y-2373, was selected by screening of various yeast cultures. The selected strain showed sufficient growth and good acid formation in media with growth-limiting concentrations of nitrogen, sulfur, phosphorus, and magnesium. A shortage of Fe2+ and Ca2+ ions suppressed both Y. lipolytica growth and formation of isocitric acid. The preferential synthesis of isocitric acid can be regulated by changing the nature and concentration of nitrogen source, pH of cultivation medium, and concentration of ester-aldehyde fraction. Experiments in this direction allowed us to obtain 65 g/L isocitric acid with a product yield (YICA) of 0.65 g/g in four days of cultivation.

Highlights

  • Over the past two decades, isocitric acid has attracted the attention of researchers as a promising compound for the pharmaceutical and food industry [1,2,3,4,5,6,7,8,9,10,11]

  • Chemical synthesis gives a mixture of four stereoisomers of isocitric acid: threoDS, threo-Ls, erythro-Ds, and erythro-Ls- [12], of which only threo-DS - or (2R,3S)-isocitric acid is a metabolite of the tricarboxilic acid (TCA) cycle used by all aerobic organisms

  • Most strains of the species Y. lipolytica excreted mainly isocitric acid (ICA), the maximum relative content of ICA (53.5% of the total amount of acids) being demonstrated by the wild strain Y. lipolytica VKM Y-2373

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Summary

Introduction

Over the past two decades, isocitric acid has attracted the attention of researchers as a promising compound for the pharmaceutical and food industry [1,2,3,4,5,6,7,8,9,10,11]. Isocitric acid beneficially influences the spatial memory of intact laboratory rats and those intoxicated with heavy metals It reduces the number of inadequate conditioned reactions and promotes the development of skills that meet new spatial conditions [8,10]. Chemical synthesis gives a mixture of four stereoisomers of isocitric acid: threoDS -, threo-Ls-, erythro-Ds-, and erythro-Ls- [12], of which only threo-DS - or (2R,3S)-isocitric acid (according to IUPAC Organic Nomenclature) is a metabolite of the tricarboxilic acid (TCA) cycle used by all aerobic organisms. It is this isomer that is commonly called isocitric acid (ICA). As for the production of naturally occurring ICA with the aid of the specially cultivated plant Sedum spectabile, the cost of ICA produced by this method is too high (USD 750 per 1g ICA) [8]

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