CLONING OF THE LATE GENES IN THE ERGOSTEROL BIOSYNTHETIC-PATHWAY OF SACCHAROMYCES-CEREVISIAE - A REVIEW

Research on the ergosterol biosynthetic pathway in fungi has focused o n the identification of the specific sterol structure required for nor mal membrane structure and function and for completion of the cell cyc le. 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 th erapeutic agents. Nine of the eleven genes in the portion of the pathw ay committed exclusively to ergosterol biosynthesis have been cloned, and their essentiality for aerobic growth has been determined. The fir st three genes, ERG9 (squalene synthase), ERG1 (squalene epoxidase), a nd ERG7 (lanosterol synthase), have been cloned and round to be essent ial for aerobic viability since their absence would result in the cell being unable to synthesize a sterol molecule. The remaining eight gen es encode enzymes which metabolize the first sterol, lanosterol, to ul timately form ergosterol. The two earliest genes, ERG11 (lanosterol de methylase) and ERG24 (C-14 reductase), have been cloned and found to b e 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 isomer ase), 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).