The regulation of reserve carbohydrate metabolism in S cerevisiae in response to nutrient availability

In Saccharomyces cerevisiae, glycogen and trehalose are important reserve carbohydrates that accumulate under nutrient limitation in batch cultures. An inherent draw-back of batch studies is that specific growth rate and substrate and product concentrations are variable over time and between cultures. The aim of this present study was to identify the nutritional requirements associated with high accumulation of reserve carbohydrates at a fixed specific growth rate (0.10 h-1) in anaerobic chemostat cultures that were limited by one of five different nutrients (carbon, nitrogen, sulfur, phosphorus or zinc). Reserve carbohydrates accumulation is not a general response to nutrient limitation. Over the conditions tested, accumulation occurs essentially under nitrogen (and to a lesser extent carbon) limited conditions. This was confirmed by the transcriptional profile of the genes involved in trehalose biosynthesis. We show that the transcriptional induction of both glycogen and trehalose biosynthesis genes was to a large extent driven by the regulator Msn2/4. However, the main regulatory control of glycogen biosynthesis was post-translational. Under nitrogen limitation, the ratio of glycogen synthase over glycogen phosphorylase increased up to eight-fold, thus enabling an increased flux towards glycogen biosynthesis. We studied this in anaerobic chemostat cultures at a dilution rate of 0.10 h-1 where growth was limited by five different nutrients (carbon, nitrogen, sulfur, phosphorus or zinc limitations). In addition, we studied the expression of these pathways at transcriptional and post-transcriptional levels and assessed the role of Msn2/4 in mediating transcriptional induction of glycogen and trehalose genes in the absence of stress.