Regulation of Sensing, Transportation, and Catabolism of Nitrogen Sources in Saccharomyces cerevisiae

Abstract

Nitrogen is one of the most important essential nutrient sources for biogenic activities. Regulation of nitrogen metabolism in microorganisms is complicated and elaborate. For this review, the yeast was chosen to demonstrate the regulatory mechanism of nitrogen metabolism because of its relative clear genetic background. Current opinions on the regulation processes of nitrogen metabolism in, including nitrogen sensing, transport, and catabolism, are systematically reviewed. Two major upstream signaling pathways, the Ssy1-Ptr3-Ssy5 sensor system and the target of rapamycin pathway, which are responsible for sensing extracellular and intracellular nitrogen, respectively, are discussed. The ubiquitination of nitrogen transporters, which is the most general and efficient means for controlling nitrogen transport, is also summarized. The following metabolic step, nitrogen catabolism, is demonstrated at two levels: the transcriptional regulation process related to GATA transcriptional factors and the translational regulation process related to the general amino acid control pathway. The interplay between nitrogen regulation and carbon regulation is also discussed. As a model system, understanding the meticulous process by which nitrogen metabolism is regulated in not only could facilitate research on global regulation mechanisms and yeast metabolic engineering but also could provide important insights and inspiration for future studies of other common microorganisms and higher eukaryotic cells.

Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi

“…TOR signaling is also required for fluconazole tolerance and full virulence in a murine model in C. neoformans [31,46]. Closely connected to TOR signaling is the general amino acid control (GAAC), which in S. cerevisiae induces amino acid biosynthesis upon starvation in a process that is mediated by the transcription factor ScGcn4 [36,47]. Similarly, CaGcn4 is required for filamentous growth in response to amino acid starvation and for full virulence in systemic model of candidiasis [32,48].…”

“…Otherwise the organism is not really clear. [36,49]. The system contains a functionally adapted, membrane-bound AAP named ScSsy1 which is activated upon increased extracellular concentrations of various amino acids, though the degree of activation varies by amino acid.…”

“…Importantly, pathogenic fungi possess multiple amino acid transporters and biosynthetic pathways This article is part of the Topical Collection on Mycology Many fungi preferentially utilize ammonium, glutamine, and glutamate as nitrogen sources, while nitrates, nitrites, purines, amides, other amino acids, and proteins are used when primary nitrogen sources are limited. The utilization of secondary nitrogen sources is directed by a global control mechanism named NCR and mediated by the GATA-type transcription factors ScGat1 and ScGln3, which positively regulate the expression of permeases and pathway-specific catabolic enzymes upon nitrogen starvation [36,38,39]. S. cerevisiae orthologs governing similar regulatory circuits are described for all three pathogenic fungi [27-30, 40, 41].…”

“…The TOR pathway represents the main sensor for the intracellular nutrient state and mediates cellular responses, including alterations in the nitrogen and amino acid metabolism. The integration of extra-and intracellular nutrient-derived signals into other signaling and regulatory pathways is mediated via the nutrient-sensitive Tor kinase ScTor1 [36,42]. Although…”

Eisosomes at the intersection of TORC1 and TORC2 regulation

“…Therefore, transcriptional regulation varies between the different transporters. Amino acid transporter expression has been studied in great detail and I refer to several comprehensive reviews for an in‐depth read on this subject . In brief, the main system that regulates the transcription of amino acid APC transporters is the SPS sensor (named after the key components Ssy1, Ptr3 and Ssy5) that is able to detect the presence of micromolar concentrations of amino acids in the medium and induces expression of the transporter genes with the help of the transcription factors Stp1 and Stp2.…”