S-Adenosyl-L-methionine (SAM) is a fine chemical used as a nutritional supplement and a prescription drug. It is industrially produced using Saccharomyces cerevisiae owing to its high SAM content. To investigate the optimization of culture medium components for higher SAM production, metabolome analysis was conducted to compare the intracellular metabolite concentrations between Kyokai no. 6 (high SAM-producing) and laboratory yeast S288C (control) under different SAM production conditions. Metabolome analysis and the result of principal component analysis showed that the rate-limiting step for SAM production was ATP supply and the levels of degradation products of adenosine nucleotides were higher in Kyokai 6 strain than in the S288C strain under the L-methionine supplemented condition. Analysis of ATP accumulation showed that the levels of intracellular ATP in the Kyokai 6 strain were also higher compared to those in the S288C strain. Furthermore, as expected from metabolome analysis, the SAM content of Kyokai 6 strain cultivated in the medium without yeast extract increased by 2.5-fold compared to that in the additional condition, by increasing intracellular ATP level with inhibited cell growth. These results suggest that high SAM production is attributed to the enhanced ATP supply with L-methionine condition and high efficiency of intracellular ATP consumption.
Keywords: Central carbon metabolism; Fermentation engineering; Metabolome analysis; S-adenosyl-L-methionine; Saccharomyces cerevisiae.