Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
Microbiology (Reading). 2010 Feb;156(Pt 2):452-462. doi: 10.1099/mic.0.030072-0. Epub 2009 Oct 29.
Inositol is essential in eukaryotes, and must be imported or synthesized. Inositol biosynthesis in Saccharomyces cerevisiae is controlled by three non-essential genes that make up the inositol regulon: ScINO2 and ScINO4, which together encode a heterodimeric transcriptional activator, and ScOPI1, which encodes a transcriptional repressor. ScOpi1p inhibits the ScIno2-ScIno4p activator in response to extracellular inositol levels. An important gene controlled by the inositol regulon is ScINO1, which encodes inositol-3-phosphate synthase, a key enzyme in inositol biosynthesis. In the pathogenic yeast Candida albicans, homologues of the S. cerevisiae inositol regulon genes are 'transcriptionally rewired'. Instead of regulating the CaINO1 gene, CaINO2 and CaINO4 regulate ribosomal genes. Another Candida species that is a prevalent cause of infections is Candida glabrata; however, C. glabrata is phylogenetically more closely related to S. cerevisiae than C. albicans. Experiments were designed to determine if C. glabrata homologues of the inositol regulon genes function similarly to S. cerevisiae or are transcriptionally rewired. CgINO2, CgINO4 and CgOPI1 regulate CgINO1 in a manner similar to that observed in S. cerevisiae. However, unlike in S. cerevisiae, CgOPI1 is essential. Genetic data indicate that CgOPI1 is a repressor that affects viability by regulating activation of a target of the inositol regulon.
肌醇在真核生物中是必不可少的，必须通过导入或合成来获取。酿酒酵母的肌醇生物合成受三个组成肌醇调控基因的非必需基因控制：ScINO2 和 ScINO4，它们共同编码一个异二聚体转录激活因子，以及 ScOPI1，它编码一个转录抑制因子。ScOpi1p 响应细胞外肌醇水平抑制 ScIno2-ScIno4p 激活物。受肌醇调控基因控制的一个重要基因是 ScINO1，它编码肌醇-3-磷酸合酶，这是肌醇生物合成的关键酶。在致病性酵母白色念珠菌中，酿酒酵母肌醇调控基因的同源物被“转录重排”。CaINO2 和 CaINO4 调节核糖体基因，而不是调节 CaINO1 基因。另一种普遍引起感染的念珠菌物种是光滑念珠菌；然而，与白色念珠菌相比，光滑念珠菌在系统发育上与酿酒酵母更为接近。设计实验来确定肌醇调控基因的光滑念珠菌同源物是否与酿酒酵母类似发挥作用，或者是否发生转录重排。CgINO2、CgINO4 和 CgOPI1 以与在酿酒酵母中观察到的相似的方式调节 CgINO1。然而，与酿酒酵母不同，CgOPI1 是必需的。遗传数据表明，CgOPI1 是一种通过调节肌醇调控基因靶标的激活来影响生存能力的抑制因子。
