title: Enhanced intracellular glutathione synthesis and excretion capability of Candida utilis by using a low pH-stress strategy.
abstract: OBJECTIVE
  To study the effect of low pH stress on glutathione (GSH) synthesis and excretion capability of GSH fermentation production in Candida utilis.
  
  
  RESULTS
  When C. utilis WSH 02-08 was cultivated in a glucose-ammonium sulfate medium without pH control, GSH leakage occurred when the pH of the medium decreased to 1.5. However, analysis of the cell viability indicated that the cells were not lysed. To further study the effect of low pH stress on GSH production, pH-controlled batch cultures were conducted, where the pH was switched from 5.5 to 1.2 at 24 h and maintained at 1.2 for 6 h. Nearly all intracellular GSH was leaked into the medium and the cell viability decreased dramatically, conceiving a long-term exposure of strain WSH 02-08 at low pH environment led to a complete cell lysis. A critical point (treated at pH 1.2 for 3 h) was experimentally determined, where most cells were alive but suffering a low pH stress. Low pH-stressed C. utilis cells displayed an increased intracellular GSH synthesis and export capability, which protected the cells against short-term low pH treatment.
  
  
  CONCLUSIONS
  Using this knowledge, a low pH-stress strategy was developed and applied in fed-batch production of GSH and 197.3 mg l-1 of GSH was secreted into the medium. The GSH-specific production yield could be increased from 2.11 to 2.67% (w/w), and the total GSH concentration could reach 737.1 mg l-1 and increased by 24.9%.
  
  
  CONCLUSIONS
  This is the first report of GSH secretion of C. utilis at low pH. This study demonstrated the importance of the physiology-based fermentation strategy in the production of useful metabolites.
authors.affiliation: Key Laboratory of Industrial Biotechnology, Ministry of Education, Southern Yangtze University, Wuxi, China.
authors.forename: W
authors.initials: W
authors.lastname: Nie
authors.forename: G
authors.initials: G
authors.lastname: Wei
authors.forename: G
authors.initials: G
authors.lastname: Du
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D002175:Candida / Q000254:growth & development / Q000378:metabolism*; D003470:Culture Media; D005285:Fermentation; D005947:Glucose; D005978:Glutathione / Q000096:biosynthesis*; D006863:Hydrogen-Ion Concentration
chemical_list: D003470:Culture Media; D005978:Glutathione; D005947:Glucose