Hydroxybenzoate metabolism in yeasts: identification and evolutionary analysis of the genes involved in the gentisate and 3-oxoapidate pathways in Candida parapsilosis

Candida parapsilosis is an emerging fungal human pathogen. It is able to degrade various hydroxy derivatives of benzenes and benzoic acid through the gentisate and 3-oxoapidate pathway. However, genes involved in these pathways remain unknown. We analyzed transcriptomes (RNAseq) of Candida parapsilosis cultivated on three carbon sources: glucose, 3- and 4-hydroxybenzoate. Among highly up-regulated genes, we identified seven possibly coding for enzymes that are involved in these pathways. Recently, some of these were confirmed. We identified candidate transcription factors regulating switch of metabolism from glucose to hydroxybenzoates. Moreover, we identified putative membrane transporters required for the uptake of hydroxybenzoates. Subsequently, the evolutionary history of the gentisate and 3-oxoapidate pathways in yeasts was analyzed. Complete pathways were found only in 5 out of the 25 sequenced Saccharomycotina species. Among these, Scheffersomyces stipitis metabolizes both hydroxybenzoates and hydroxybenzenes. The remaining four, Candida parapsilosis and other three Candida species recently sequenced by us, are emerging human pathogens. This suggests that the gentisate and 3-oxoapidate pathways may play a role in pathogenesis.