Soustre I, Girard P, Karst F
Laboratoire de Génétique Physiologique et Moléculaire, Université de Poitiers, IBMIG.
C R Seances Soc Biol Fil. 1998;192(5):977-90.
The yeast Saccharomyces cerevisiae was a powerful tool in the identification of the structural genes involved in sterol biosynthesis in eucaryotes. Among 20 genes, 16 were isolated by genetic techniques using either complementation of mutants or overexpression strategy using specific inhibitors. In spite of this good knowledge concerning the genes of the pathway, little is known about the regulation of the isoprenoid/steroid biosynthetic pathway. However, the existence of two genes encoding HMG-CoA reductase in yeast genome suggests strongly that this enzyme could play a fundamental function in regulation, such as in plants and mammals. The regulation mechanisms could also involve sterol trafficking and storage. Indeed, one enzyme in the pathway, the sterol-C24-methyl transferase is localized in lipid particles that correspond to the storage form of steryl esters. Yeast cells are impermeable towards exogenous sterols in aerobiosis and become permeable in anaerobiosis when ergosterol synthesis is precluded by the absence of molecular oxygen. This phenomenon called aerobic sterol exclusion is dependent on the hem status of the cell. One gene, named SUT1 was identified that directs aerobic sterol uptake in yeast SUT1 gene and his partner SUT2 present strong features common to yeast transcription factors and could regulate the expression of genes involved in sterol uptake or intracellular trafficking.
酿酒酵母是鉴定真核生物中参与甾醇生物合成的结构基因的有力工具。在20个基因中，16个是通过遗传技术分离得到的，这些技术要么是利用突变体的互补作用，要么是使用特定抑制剂的过表达策略。尽管对该途径的基因有了很好的了解，但关于类异戊二烯/类固醇生物合成途径的调控却知之甚少。然而，酵母基因组中存在两个编码HMG-CoA还原酶的基因，这强烈表明该酶可能在调控中发挥基本功能，就像在植物和哺乳动物中一样。调控机制也可能涉及甾醇的运输和储存。事实上，该途径中的一种酶，即甾醇-C24-甲基转移酶，定位于与甾醇酯储存形式相对应的脂质颗粒中。酵母细胞在需氧条件下对外源甾醇是不可渗透的，而在厌氧条件下，当分子氧的缺乏阻止麦角甾醇合成时，酵母细胞就会变得可渗透。这种称为需氧甾醇排除的现象取决于细胞的血红素状态。一个名为SUT1的基因被鉴定出来，它指导酵母中的需氧甾醇摄取。SUT1基因及其伙伴SUT2具有酵母转录因子共有的强大特征，并且可以调节参与甾醇摄取或细胞内运输的基因的表达。
