Biotechnology for production of bioactive seleno compounds and study of their influence on mouse metabolome

Conference poster, 2011

Organic seleno compounds are recognized as effective anti-oxidant agents and their bioactive role in prevention of certain forms of cancer has been suggested via in vitro studies and clinical trials. Among these compounds, Seleno-methyselenocysteine (SeMCys) and γ-glutamyl-SeMCys (γ-glu-SeMCys) are the most bioactive and the latter is the preferred storage form of selenium in Se-accumulator plants thanks to their Se-methyltransferase. Therefore, Se-accumulator edible plants such as Brassicaceae and Allioideae are the main source of SeMCys and γ-glu-SeMCys in the human diet. However, seasonal and environmental factors highly affect the content and the bioavailability of these bioactive compounds. A strategy to by-pass this problem and prevent selenium shortage in human diet is the production of Se-enriched yeast (Se-yeast) to be used as food supplement. In this work we show a biotechnological approach for production Se-yeast featured by higher content of SeMCys and γ-glu-SeMCys. Coupling of metabolic engineering and bioprocess optimization resulted in a Se-yeast with 24-fold increase of SeMCys levels, compared to commercial Se-yeast. The actual effect of the produced yeast has been evaluated in an animal study. In particular, as specific Se-compounds are known to activate phase II enzymes via the electrophile-responsive element (EpRE), this response was studied in transgenic mice expressing the luciferase gene under EpRE control. We observed no effect on regulation of EpRE, either overall or hepatic, by the different Se-supplements. Paradoxically, a decrease was observed in intestinal EpRE transactivation upon supplementation of the Se-yeast produced. The overall effect of the diet supplemented with Se-yeast on mouse metabolism is currently being evaluated by metabolome analysis of liver samples from the transgenic mice.