The present state of knowledge of ergosterol biosynthesis is reviewed briefly in order to provide a contextual framework for the following papers which deal with its inhibition, the compounds that cause this inhibition, and their mode of action. The paper concentrates upon the post-squalene segment of the process as it occurs in fungi because the commercially important inhibitors of ergosterol biosynthesis are fungicides that block steps within that process.

The Biosynthesis of Ergosterol

The typical plant sterols contain a substituent at C-24 of the side chain. This can be a methylene, ethylidene, methyl, or ethyl group; with the last three groups, all possible isomers have been reported in nature. The C-24 alkyl groups are derived by a transmethylation reaction from methionine. The details of several distinct alkylation mechanisms, which are now recognized in a range of lower and higher plants, have been reviewed. The operation of these different routes may have some phylogenetic significance.

Phytosterol side chain biosynthesis.

Four new and other 4α-methylsterols in the seeds of Solanaceae

Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis by oxylanosterols.

The sterol components of the Rhodophyceae, Porphyridium cruentum and Porphyridium aerugineum have been investigated. The 4α-methyl sterol fraction of P. cruentum contained two novel sterols, 4α-methyl-5α-cholesta-8,22-dien-3β-ol and 4α,24ζ-dimethyl-5α-cholesta-8,22-dien-3β-ol, together with 4α-methyl-5α-cholest-8-en-3β-ol, 4α,24ζ-dimethyl-5α-cholest-8-en-3β-ol and obtusifoliol. It is particularly significant that the two new sterols are the first reported 4-methyl sterols to contain δ22 unsaturation. Broken cell preparations of both organisms cyclized squalene-2,3-oxide exclusively to cycloartenol. A possible biosynthetic pathway based on the structures of all the sterols isolated from P. cruentum is proposed, which allows for the introduction of δ22 unsaturation at the 4α-methyl level.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1974.tb03270.x

Sterols in Porphyridium Species

24,25-Dihydro-24-methylenelanosterol has been synthesised from lanosterol and investigated as a potential precursor of eburicoic acid and of ergosterol.Two new sterols, 24,25-dihydro-4α-methyl-24-methylenezymosterol and 3β-hydroxy-4α-methylcholesta-8(14),24-diene have been isolated from yeast residues and their structures have been determined. The constitution of 24,25-dihydro-4α-methyl-24-methylenezymosterol has been confirmed by a partial synthesis from the more abundant 4α-methylzymosterol.4α-Methylzymosterol, 24,25-dihydro-4α-methyl-24-methylenezymosterol and obtusifoliol have been shown to be incorporated into ergosterol in yeast cultures. 4,4-Dimethylergosterol is, however, not a precursor.By a trapping experiment in which tritium-labelled squalene oxide and unlabelled 24,25-dihydro-24-methylene-lanosterol were used it has been shown that the latter is almost certainly not on the biogenetically preferred route from lanosterol to ergosterol.

Investigations on the biosynthesis of steroids and terpenoids. Part II. Role of 24-methylene derivatives in the biosynthesis of steroids and terpenoids

D. M. Harrison

Papers

Investigations on the biosynthesis of steroids and terpenoids. Part II. Role of 24-methylene derivatives in the biosynthesis of steroids and terpenoids

Biosynth. von steroiden und terpenoiden 2. mitt. 24‐methylenderivate in der biosynth. von steroiden und terpenoiden