The common brewer’s yeast, Saccharomyces cerevisiae, is arguably one of the most important industrial microbes. It is used for the production of fermented foods and beverages like bread, beer and wine, as well as bio-ethanol, enzymes and pharmaceuticals. However, some of the natural characteristics of Saccharomyces cerevisiae are not optimal in industrial setting. In particular, when Saccharomyces cerevisiae is grown in media containing glucose, the cells shut down the uptake of other carbon sources found in industrial growth media, a process called “glucose repression”. In addition, glucose also affects the expression of genes related to other cellular functions such as respiration, gluconeogenesis, and stress response mechanisms. The repression of respiration in Saccharomyces yeasts growing in glucose explains why Saccharomyces cerevisiae ferments (and not respires) glucose even in the presence of oxygen, a phenomenon called “Crabtree effect". Because fermentation yields less energy than respiration, the Crabtree effect implies that the energy yield in high glucose concentrations are sub-optimal. Moreover, when cells need to switch between glucose and another carbon source, they stop growing and all but arrest their metabolism, entering a so-called lag phase, which further reduces the efficiency of production processes where glucose and other sugars are mixed.
In our ongoing ERC project, we found that the Crabtree effect is a central limiting factor in industrial applications because it limits the efficiency of biomass production for companies that produce yeast, and also limits fermentation efficiency for companies that produce fermented products like beer, wine, bread and bioethanol. Moreover, we discovered that natural variation in the Saccharomyces cerevisiae gene YLR108C results in different levels of Crabtree repression and/or different durations of the lag phase. In this POC project we investigated whether we can exploit this discovery to breed or engineer industrial yeasts that show increased production efficiency when growing on media that contain glucose and other carbon sources, such as for example beer wort. The results show that manipulating YLR108C can help boost efficient biomass production, helping to maintain aerobic respiratory growth even at higher sugar concentrations. Changing YLR108C also shows some influence on fermentation performance, but these results are not completely conclusive and merit further research.
