Abstract
BackgroundSaccharomyces cerevisiae is a host for the industrial production of S-adenosyl-l-methionine (SAM), which has been widely used in pharmaceutical and nutritional supplement industries. It has been reported that the intracellular SAM content in S. cerevisiae can be improved by the addition of ethanol during cultivation. However, the metabolic state in ethanol-assimilating S. cerevisiae remains unclear. In this study, 13C-metabolic flux analysis (13C-MFA) was conducted to investigate the metabolic regulation responsible for the high SAM production from ethanol.ResultsThe comparison between the metabolic flux distributions of central carbon metabolism showed that the metabolic flux levels of the tricarboxylic acid cycle and glyoxylate shunt in the ethanol culture were significantly higher than that of glucose. Estimates of the ATP balance from the 13C-MFA data suggested that larger amounts of excess ATP was produced from ethanol via increased oxidative phosphorylation. The finding was confirmed by the intracellular ATP level under ethanol-assimilating condition being similarly higher than glucose.ConclusionsThese results suggest that the enhanced ATP regeneration due to ethanol assimilation was critical for the high SAM accumulation.
Highlights
Saccharomyces cerevisiae is a host for the industrial production of S-adenosyl-l-methionine (SAM), which has been widely used in pharmaceutical and nutritional supplement industries
While the transcriptome analysis of S. cerevisiae grown on ethanol indicated the transcripts related to gluconeogenesis, the glyoxylate shunt, and the tricarboxylic acid (TCA) cycle were upregulated compared with those grown on glucose [6], the in vivo activity of the metabolic pathway involved in the SAM accumulation under ethanol-assimilating condition is still far from clear
The results showed that the metabolic flux levels through the glyoxylate shunt and the later TCA cycle were upregulated during growth on ethanol, and the resultant activation of the oxidative phosphorylation should contribute the high SAM accumulation in the ethanol-assimilating conditions
Summary
Saccharomyces cerevisiae is a host for the industrial production of S-adenosyl-l-methionine (SAM), which has been widely used in pharmaceutical and nutritional supplement industries. It has been reported that the intracellular SAM content in S. cerevisiae can be improved by the addition of ethanol during cultivation. Saccharomyces cerevisiae has been used in several industrial processes such as for the production of S-adenosyll-methionine (SAM) [1, 2]. While the transcriptome analysis of S. cerevisiae grown on ethanol indicated the transcripts related to gluconeogenesis, the glyoxylate shunt, and the tricarboxylic acid (TCA) cycle were upregulated compared with those grown on glucose [6], the in vivo activity of the metabolic pathway involved in the SAM accumulation under ethanol-assimilating condition is still far from clear
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