The type of carbon source not the growth rate it supports can determine diauxie

How cells choose between potential carbon sources is a classic example of cellular decision-making, and we know that many organisms prioritise glucose. Yet there has been little investigation of whether other sugars are also preferred, blinkering our view of carbon sensing. Here we study eukaryotic budding yeast and its growth on mixtures of sugars with palatinose, an isomer of sucrose that cells catabolise with the MAL regulon. We find that yeast prioritise galactose over palatinose, but sucrose and fructose only weakly if at all, despite each sugar being able to support faster growth than palatinose. Our results therefore suggest that the decision-making is more than carbon flux-sensing. By using genetic perturbations and transcriptomics, we show that there is repression of the MAL genes via Gal4, the master regulator of the GAL regulon. Mechanistically, cells enforce their preference for galactose over palatinose through preventing runaway positive feedback in the MAL regulon. They do so both by repressing MAL11, the gene encoding the palatinose transporter, and by early expression of the isomaltases IMA1 and IMA5. By cleaving palatinose, these enzymes prevent its intracellular concentration becoming sufficient to induce further MAL expression. Our results demonstrate that budding yeast actively maintain a preference for carbon sources other than glucose and that such preferences have been selected by more than differences in growth rates. They imply that carbon-sensing strategies even in unicellular organisms are more complex than previously thought.