Cellular responses to L-serine in Saccharomyces cerevisiae: Roles of general amino acid control, compartmentalization, and aspartate synthesis

Abstract

In addition to its other roles, l-serine functions in one-carbon metabolism and is interconvertable with glycine via serine hydroxymethyltransferases. However, the transcriptional response by Saccharomyces cerevisiae to l-serine addition is markedly different from that to glycine, with l-serine acting as a nutrient source rather than one-carbon units. Following addition of excess l-serine, 743 genes showed significant expression changes. Induced functions included amino acid synthesis, some stress responses, and FeS metabolism, while ribosomal RNA processing, ribosome biogenesis and hexose transport were repressed. A co-regulated network of ten transcription factors could together control more than 90% of the induced and repressed genes forming a general response to changes induced by other amino acids or stresses and including the general amino acid control system usually activated in response to starvation for amino acids. A specific response to l-serine was induction of CHA1 encoding serine (threonine) dehydratase. l-serine addition resulted in a substantial transient increase in l-aspartate, which is, rather than l-glutamate, the major metabolite for short-term storage of ammonia derived from degradation of l-serine. l-aspartate synthesis was exclusively through mitochondrial metabolism of l-serine to pyruvate and ammonia, involving Cha1p, cytoplasmic pyruvate carboxylases Pyc1p and Pyc2p, and the cytoplasmic aspartate aminotransferase Aat2p. © 2013 Federation of European Microbiological Societies.