Metabolome analysis of Saccharomyces cerevisiae and optimization of culture medium for S-adenosyl-l-methionine production

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13568-016-0210-3) contains supplementary material, which is available to authorized users.

Lactobacillus acidophilus DDS-1 Modulates the Gut Microbiota and Improves Metabolic Profiles in Aging Mice

“…A MetaboAnalyst (Version 4.0) data annotation approach and Kyoto Encyclopaedia of Genes and Genomes (KEGG) Pathway Database were used for the hierarchical clustering analysis and significance analysis for microarrays (SAM), along with the variable importance of projection (VIP) [ 42 ]. The SAM and VIP methods are well-established statistical methods for metabolites and were used to select the most discriminant and interesting biomarkers [ 43 ].…”

Lipid Composition of Sheffersomyces stipitis M12 Strain Grown on Glycerol as a Carbon Source

“…It seems that for both types of S. stipitis strains tested in this work, β-oxidation is a prominent pathway and the most important source for ATP, needed in the SAM production. Moreover, metabolome analysis provided by Hayakawa et al ( 44 ) showed that the level of intracellular ATP was depleted in the methionine-supplemented medium. In order to ensure effective SAM production, the increase of ATP supply is crucial.…”

13C-metabolic flux analysis of ethanol-assimilating Saccharomyces cerevisiae for S-adenosyl-l-methionine production

“…The addition of sodium citrate improved the isocitric acid dehydrogenase activity and ATP level in the cell, which promoted the conversion of methionine into SAM [ 39 ]. Optimization of the culture medium also revealed that the restriction of cell growth, and the enhancement of the intracellular ATP level and SAM production were achieved by reducing the supplemented yeast extract [ 8 ]. Moreover, the result of this study that the intracellular l -methionine level in ethanol assimilating was higher than that of glucose (Fig.…”

“…The intracellular ATP, l -methionine, and SAM concentrations were measured using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) according to previously described methods [ 8 ]. Cultivated cells were harvested by filtration and washed with Milli-Q water.…”