Optimization of glutathione production in batch and fed-batch cultures by the wild-type and recombinant strains of the methylotrophic yeast Hansenula polymorphaDL-1

BMC Biotechnology

Research Article

Alexander Y Malyshev¹  Vira M Ubiyvovk²  Andriy A Sibirny³  Vladimir M Ananin⁴  Hyun Ah Kang⁵ 

[1] Institute of Cell Biology NAS of Ukraine, Drahomanov Street, 14/16, 79005, Lviv, Ukraine;Institute of Cell Biology NAS of Ukraine, Drahomanov Street, 14/16, 79005, Lviv, Ukraine;Korea Research Institute of Bioscience and Biotechnology, 305-333, Daejeon, Korea;Institute of Cell Biology NAS of Ukraine, Drahomanov Street, 14/16, 79005, Lviv, Ukraine;University of Rzeszow, Cwiklinskiej 2, 35-601, Rzeszow, Poland;Korea Research Institute of Bioscience and Biotechnology, 305-333, Daejeon, Korea;Korea Research Institute of Bioscience and Biotechnology, 305-333, Daejeon, Korea;Department of Life Science, Chung-Ang University, 156-756, Heukseok-dong, Dongjak-gu, Seoul, Korea;

关键词: Recombinant Strain;    Dissolve Oxygen Tension;    Methylotrophic Yeast;    Stirrer Speed;    Glucose Feeding;   

DOI  :  10.1186/1472-6750-11-8

 received in 2010-08-11, accepted in 2011-01-22,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundTripeptide glutathione (gamma-glutamyl-L-cysteinyl-glycine) is the most abundant non-protein thiol that protects cells from metabolic and oxidative stresses and is widely used as medicine, food additives and in cosmetic industry. The methylotrophic yeast Hansenula polymorpha is regarded as a rich source of glutathione due to the role of this thiol in detoxifications of key intermediates of methanol metabolism. Cellular and extracellular glutathione production of H. polymorpha DL-1 in the wild type and recombinant strains which overexpress genes of glutathione biosynthesis (GSH2) and its precursor cysteine (MET4) was studied.ResultsGlutathione producing capacity of H. polymorpha DL-1 depending on parameters of cultivation (dissolved oxygen tension, pH, stirrer speed), carbon substrate (glucose, methanol) and type of overexpressed genes of glutathione and its precursor biosynthesis during batch and fed-batch fermentations were studied. Under optimized conditions of glucose fed-batch cultivation, the glutathione productivity of the engineered strains was increased from ~900 up to ~ 2300 mg of Total Intracellular Glutathione (TIG) or GSH+GSSGin, per liter of culture medium. Meantime, methanol fed-batch cultivation of one of the recombinant strains allowed achieving the extracellular glutathione productivity up to 250 mg of Total Extracellular Glutathione (TEG) or GSH+GSSGex, per liter of the culture medium.ConclusionsH. polymorpha is an competitive glutathione producer as compared to other known yeast and bacteria strains (Saccharomyces cerevisiae, Candida utilis, Escherichia coli, Lactococcus lactis etc.) with good perspectives for further improvement especially for production of extracellular form of glutathione.

【 授权许可】

Unknown   
© Ubiyvovk et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.