CLONING OF THE LATE GENES IN THE ERGOSTEROL BIOSYNTHETIC-PATHWAY OF SACCHAROMYCES-CEREVISIAE - A REVIEW
CLONING OF THE LATE GENES IN THE ERGOSTEROL BIOSYNTHETIC-PATHWAY OF SACCHAROMYCES-CEREVISIAE - A REVIEW
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作者：
LEES, ND;SKAGGS, B;BARD, M
真菌中麦角固醇生物合成途径的研究集中在鉴定正常膜结构和功能以及完成细胞周期所需的特定固醇结构。该途径及其终产物也是许多抗真菌药物的靶点。确定麦角甾醇生物合成的关键步骤可以为开发新的治疗药物提供新的靶点。已克隆了途径中专门用于麦角固醇生物合成的11个基因中的9个，并确定了它们对需氧生长的重要性。前三个基因，ERG 9（角鲨烯合酶），ERG 1（角鲨烯环氧酶），和ERG 7（羊毛甾醇合酶），已被克隆和轮是有氧活力所必需的，因为它们的缺乏将导致细胞不能合成甾醇分子。剩下的8个基因编码代谢第一个甾醇羊毛甾醇最终形成麦角甾醇的酶。两个最早的基因，ERG 11（羊毛甾醇脱甲基酶）和ERG 24（C-14还原酶），已被克隆，并发现是必要的有氧生长，但抑制C-5去饱和酶（ERG 3）基因突变和fen 1和fen 2突变，分别。已发现其余克隆基因ERG 6（C-24甲基化酶）、ERG 2（D8 AE 7异构酶）、ERG 3（C-5去饱和酶）和ERG 4（C-24（28）还原酶）是非必需的。其余尚未克隆的基因是C-4脱甲基酶和C-22去饱和酶（ERG 5）。
Research on the ergosterol biosynthetic pathway in fungi has focused on the identification of the specific sterol structure required for normal membrane structure and function and for completion of the cell cycle. The pathway and its end product are also the targets for a number of antifungal drugs. Identification of essential steps in ergo-sterol biosynthesis could provide new targets for the development of novel therapeutic agents. Nine of the eleven genes in the portion of the pathway committed exclusively to ergosterol biosynthesis have been cloned, and their essentiality for aerobic growth has been determined. The first three genes, ERG9 (squalene synthase), ERG1 (squalene epoxidase), and ERG7 (lanosterol synthase), have been cloned and round to be essential for aerobic viability since their absence would result in the cell being unable to synthesize a sterol molecule. The remaining eight genes encode enzymes which metabolize the first sterol, lanosterol, to ultimately form ergosterol. The two earliest genes, ERG11 (lanosterol demethylase) and ERG24 (C-14 reductase), have been cloned and found to be essential for aerobic growth but are suppressed by mutations in the C-5 desaturase (ERG3) gene and fen1 and fen2 mutations, respectively. The remaining cloned genes, ERG6 (C-24 methylase), ERG2 (D8 AE7 isomerase), ERG3 (C-5 desaturase), and ERG4 (C-24(28) reductase), have been found to be nonessential. The remaining genes not yet cloned are the C-4 demethylase and the C-22 desaturase (ERG5).