Applied Microbiology and Biotechnology

, Volume 103, Issue 8, pp 3549–3558 | Cite as

Biosynthesis of isocitric acid in repeated-batch culture and testing of its stress-protective activity

  • Igor G. MorgunovEmail author
  • Svetlana V. Kamzolova
  • Olga V. Karpukhina
  • Svetlana B. Bokieva
  • Anatoly N. Inozemtsev
Applied microbial and cell physiology


Biosynthesis of Ds(+)-threo-isocitric acid from ethanol in the Yarrowia lipolytica batch and repeated-batch cultures was studied. Repeated-batch cultivation was found to provide for a good biosynthetic efficiency of the producer for as long as 748 h, probably due to maintenance of high activities of enzymes involved in the biosynthesis of isocitric acid. Under optimal repeated-batch cultivation conditions, the producer accumulated 109.6 g/L Ds(+)-threo-isocitric acid with a production rate of 1.346 g/L h. The monopotassium salt of isocitric acid isolated from the culture liquid and purified to 99.9% was found to remove neurointoxication, to restore memory, and to improve the learning of laboratory rats intoxicated with lead and molybdenum salts. Taking into account the fact that the neurotoxic effect of heavy metals is mainly determined by oxidative stress, the aforementioned favorable action of isocitric acid on the intoxicated rats can be explained by its antioxidant activity among other pharmacological effects.


Microbial synthesis Ds(+)-threo-isocitric acid Repeated-batch cultivation Antioxidants Stress-protective activity 


Funding information

The reported research was funded by the Russian Foundation for Basic Research and the government of the Moscow Region of the Russian Federation, grant № 17-48-500446.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Center for Biological Research of the Russian Academy of Sciences”PushchinoRussia
  2. 2.Department of Higher Nervous Activity, Faculty of BiologyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Semenov Institute of Chemical Physics, Russian Academy of SciencesMoscowRussia
  4. 4.Khetagurov North Ossetian State UniversityVladikavkazRussia

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