Rewiring of the Ppr1 Zinc Cluster Transcription Factor from Purine Catabolism to Pyrimidine Biogenesis in the Saccharomycetaceae.
Metabolic pathways are largely conserved in eukaryotes, but the transcriptional regulation of these pathways can sometimes vary between species; this has been termed "rewiring." Recently, it has been established that in the Saccharomyces lineage starting from Naumovozyma castellii, genes involved in allantoin breakdown have been genomically relocated to form the DAL cluster. The formation of the DAL cluster occurred along with the loss of urate permease (UAP) and urate oxidase (UOX), reducing the requirement for oxygen and bypassing the candidate Ppr1 inducer, uric acid. In Saccharomyces cerevisiae, this allantoin catabolism cluster is regulated by the transcription factor Dal82, which is not present in many of the pre-rearrangement fungal species. We have used ChIP-chip analysis, transcriptional profiling of an activated Ppr1 protein, bioinformatics, and nitrogen utilization studies to establish that in Candida albicans the zinc cluster transcription factor Ppr1 controls this allantoin catabolism regulon. Intriguingly, in S. cerevisiae, the Ppr1 ortholog binds the same DNA motif (CGG(N6)CCG) as in C. albicans but serves as a regulator of pyrimidine biosynthesis. This transcription factor rewiring appears to have taken place at the same phylogenetic step as the formation of the rearranged DAL cluster. This transfer of the control of allantoin degradation from Ppr1 to Dal82, together with the repositioning of Ppr1 to the regulation of pyrimidine biosynthesis, may have resulted from a switch to a metabolism that could exploit hypoxic conditions in the lineage leading to N. castellii and S. cerevisiae.
Chemistry and Biochemistry Department, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada.
Walters Aji
WA
Tebung
Biology Department, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada.
Baharul I
BI
Choudhury
Infectious Diseases Research Centre (CRI), CHU de Québec Research Center (CHUQ), Université Laval, Quebec City, QC G1V 0A6, Canada.
Faiza
F
Tebbji
Institut für Molekulare Infektionsbiologie, Universität Würzburg, 97070 Würzburg, Germany.
Joachim
J
Morschhäuser
Biology Department, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada. Electronic address: malcolm.whiteway@concordia.ca.
Malcolm
M
Whiteway
D000481:Allantoin / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000096:biosynthesis*; D004718:Saccharomycetales / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011687:Purines; D011743:Pyrimidines; D015534:Trans-Activators; D014157:Transcription Factors; D000481:Allantoin; C030986:pyrimidine