Computational modeling and in silico analysis of differential regulation of myo-inositol catabolic enzymes in Cryptococcus neoformans

BACKGROUND: Inositol is a key cellular metabolite for many organisms. Cryptococcus neoformans is an opportunistic pathogen which primarily infects the central nervous system, a region of high inositol concentration, of immunocompromised individuals. Through the use of myo-inositol oxygenase C. neoformans can catabolize inositol as a sole carbon source to support growth and viability. RESULTS: Three myo-inositol oxygenase gene sequences were identified in the C. neoformans genome. Differential regulation was suggested by computational analyses of the three gene sequences. This included examination of the upstream regulatory regions, identifying ORE/TonE and UAS(INO) sequences, conserved introns/exons, and in frame termination sequences. Homology modeling of the proteins encoded by these genes revealed key differences in the myo-inositol active site. CONCLUSION: The results suggest there are two functional copies of the myo-inositol oxygenase gene in the C. neoformans genome. The functional genes are differentially expressed in response to environmental inositol concentrations. Both the upstream regulatory regions of the genes and the structure of the specific proteins suggest that MIOX1 would function when inositol concentrations are low, whereas MIOX2 would function when inositol concentrations are high.