Identification and characterization of a sulfite reductase gene and new insights regarding the sulfur-containing amino acid metabolism in the basidiomycetous yeast Cryptococcus neoformans

The amino acid biosynthetic pathway of invasive pathogenic fungi has been studied as a potential antifungal drug target. Studies of the disruption of genes involved in amino acid biosynthesis have demonstrated the importance of this pathway in the virulence of Cryptococcus neoformans . Here, we identified the MET5 ( CNL05500 ) and MET10 ( CNG03990 ) genes in this pathway, both encoding sulfite reductase, which catalyzes the reduction of sulfite to sulfide. The MET14 ( CNE03880 ) gene was also identified, which is responsible for the conversion of sulfate to sulfite. The use of cysteine as a sulfur source led to the production of methionine via hydrogen sulfide synthesis mediated by CYS4 ( CNA06170 ) , CYS3 ( CNN01730 ), and MST1 ( CND03690 ). MST1 exhibited high homology with the TUM1 gene of Saccharomyces cerevisiae , which has functional similarity with the 3-mercaptopyruvate sulfurtransferase ( 3-MST ) gene in humans. Although the hypothesis that hydrogen sulfide is produced from cysteine via CYS4 , CYS3 , and MST1 warrants further study, the new insight into the metabolic pathway of sulfur-containing amino acids in C. neoformans provided here indicates the usefulness of this system in the development of screening tools for antifungal drug agents.