Exploration of sulfur metabolism in the yeast Kluyveromyces lactis

Hemiascomycetes are separated by considerable evolutionary distances and, as a consequence, the mechanisms involved in sulfur metabolism in the extensively studied yeast, Saccharomyces cerevisiae , could be different from those of other species of the phylum. This is the first time that a global view of sulfur metabolism is reported in the biotechnological yeast Kluyveromyces lactis . We used combined approaches based on transcriptome analysis, metabolome profiling, and analysis of volatile sulfur compounds (VSCs). A comparison between high and low sulfur source supplies, i.e., sulfate, methionine, or cystine, was carried out in order to identify key steps in the biosynthetic and catabolic pathways of the sulfur metabolism. We found that sulfur metabolism of K. lactis is mainly modulated by methionine. Furthermore, since sulfur assimilation is highly regulated, genes coding for numerous transporters, key enzymes involved in sulfate assimilation and the interconversion of cysteine to methionine pathways are repressed under conditions of high sulfur supply. Consequently, as highlighted by metabolomic results, intracellular pools of homocysteine and cysteine are maintained at very low concentrations, while the cystathionine pool is highly expandable. Moreover, our results suggest a new catabolic pathway for methionine to VSCs in this yeast: methionine is transaminated by the ARO8 gene product into 4-methylthio-oxobutyric acid (KMBA), which could be exported outside of the cell by the transporter encoded by PDR12 and demethiolated by a spontaneous reaction into methanethiol and its derivatives.