Metabolic gene clusters encoding the enzymes of two branches of the 3-oxoadipate pathway in the pathogenic yeast Candida albicans.
The pathogenic yeast Candida albicans utilizes hydroxyderivatives of benzene via the catechol and hydroxyhydroquinone branches of the 3-oxoadipate pathway. The genetic basis and evolutionary origin of this catabolic pathway in yeasts are unknown. In this study, we identified C. albicans genes encoding the enzymes involved in the degradation of hydroxybenzenes. We found that the genes coding for core components of the 3-oxoadipate pathway are arranged into two metabolic gene clusters. Our results demonstrate that C. albicans cells cultivated in media containing hydroxybenzene substrates highly induce the transcription of these genes as well as the corresponding enzymatic activities. We also found that C. albicans cells assimilating hydroxybenzenes cope with the oxidative stress by upregulation of cellular antioxidant systems such as alternative oxidase and catalase. Moreover, we investigated the evolution of the enzymes encoded by these clusters and found that most of them share a particularly sparse phylogenetic distribution among Saccharomycotina, which is likely to have been caused by extensive gene loss. We exploited this fact to find co-evolving proteins that are suitable candidates for the missing enzymes of the pathway.
Departments of Biochemistry and Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-1 and B-1, 842 15 Bratislava, Slovakia.
Gabriela
G
Gérecová
Departments of Biochemistry and Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-1 and B-1, 842 15 Bratislava, Slovakia.
Martina
M
Neboháčová
Departments of Biochemistry and Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-1 and B-1, 842 15 Bratislava, Slovakia.
Igor
I
Zeman
Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Doctor Aiguader 88, 08003 Barcelona, Spain Departament de Ciències Experimentals I de la Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Leszek P
LP
Pryszcz
Departments of Biochemistry and Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-1 and B-1, 842 15 Bratislava, Slovakia.
Ľubomír
Ľ
Tomáška
Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Doctor Aiguader 88, 08003 Barcelona, Spain Departament de Ciències Experimentals I de la Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain.
Toni
T
Gabaldón
Departments of Biochemistry and Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-1 and B-1, 842 15 Bratislava, Slovakia nosek@fns.uniba.sk.
Jozef
J
Nosek
D000272:Adipates / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D001711:Biotransformation; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism*; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D023061:Gene Order; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D005810:Multigene Family; D018384:Oxidative Stress; D019800:Phenol / Q000378:metabolism*; D010802:Phylogeny; D026801:Synteny
D000272:Adipates; D000975:Antioxidants; D004798:Enzymes; C027316:3-oxoadipic acid; D019800:Phenol
catabolism of phenols; comparative genomics; evolution of biochemical pathways; gene clustering; gene expression