4.5 Article

Disruption of por1 gene in Candida utilis improves co-production of S-adenosylmethionine and glutathione

Journal

JOURNAL OF BIOTECHNOLOGY
Volume 290, Issue -, Pages 16-23

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jbiotec.2018.12.005

Keywords

S-adenosylmethionine; Glutathione; Candida utilis; por1 gene disruption; Energy supply

Funding

  1. National Natural Science Foundation of China [21376155, 21506136]
  2. Suzhou Applied Fundamental Research Program [SNG201606]
  3. Priority Academic Program Development of Jiangsu Higher Education Institutions
  4. Qing Lan Project of Jiangsu Province

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The por1 gene encoding one of the mitochondrial porin channels in C. utilis CCTCC M 209298 was disrupted using a homologous recombination method. The co-production of S-adenosylmethionine (SAM) and glutathione (GSH) in the mutant C. utilis Delta por1 increased by 34.9% and 25.1%, respectively, during batch and fed-batch fermentation, relative to the parental strain. The average oxygen consumption rate, activities of key enzymes involved in SAM and GSH biosynthesis, levels of intracellular cofactors such as NADH and ATP, and carbon fluxes of key metabolites were compared between the parental strain and the Delta por1 mutant. The disruption of por1 gene increased the rate of mitochondrial respiration, increased the activities of both methionine adeno- syltransferase and gamma-glutamylcysteine synthetase, and enhanced the supply of energy and substrates for SAM and GSH biosynthesis, all of which favored the overproduction of SAM and GSH in the Delta por1 mutant.

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