Mackenzie Emalee A, Klig Lisa S
Department of Biological Sciences, California State University, Long Beach, CA, USA.
BMC Mol Biol. 2008 Oct 14;9:88. doi: 10.1186/1471-2199-9-88.
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.
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 UASINO 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.
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.
肌醇是许多生物体中的关键细胞代谢物。新型隐球菌是一种机会性病原体，主要感染免疫功能低下个体的中枢神经系统，该区域肌醇浓度较高。通过使用肌醇加氧酶，新型隐球菌可以将肌醇作为唯一碳源进行分解代谢，以支持其生长和生存能力。
在新型隐球菌基因组中鉴定出三个肌醇加氧酶基因序列。对这三个基因序列的计算分析表明存在差异调控。这包括对上游调控区域的检查、鉴定ORE/TonE和UASINO序列、保守的内含子/外显子以及读框终止序列。对这些基因编码的蛋白质进行同源建模揭示了肌醇活性位点的关键差异。
结果表明新型隐球菌基因组中存在两个功能性的肌醇加氧酶基因拷贝。功能性基因会根据环境肌醇浓度进行差异表达。基因的上游调控区域和特定蛋白质的结构均表明，当肌醇浓度较低时MIOX1发挥作用，而当肌醇浓度较高时MIOX2发挥作用。
