Metabolic and Bioprocess Engineering for Production of selenized yeast with increased content of seleno-methylselenocysteine
Journal article, 2011
Specific Se-metabolites have been recognized as main responsible for beneficial effects of Se-enriched diet and Se-methylselenocysteine (SeMCys) is thought to be among the most effective ones. Here we show that an engineered Saccharomyces cerevisiae strain expressing a codon optimized heterologous selenocysteine-methyltransferase and endowed with high intracellular levels of S-adenosyl-methionine was able to accumulate SeMCys at levels higher than commercial selenized yeasts. A fine tuned carbon- and sulphate-limited fed-batch bioprocess was crucial to achieve good yields of biomass and SeMCys. Through the coupling of metabolic and bioprocess engineering we achieved a ~24-fold increase in SeMCys, compared to certified reference material of selenized yeast. In addition, we investigated the interplay between sulphur and selenium metabolism and the possibility that redox imbalance occurred along with intracellular accumulation of Se. Collectively, our data show how the combination of metabolic and bioprocess engineering can be used for the production of selenized yeast enriched with beneficial Se-metabolites.