Effect of squalene synthase gene disruption on synthesis of polyprenols in Saccharomyces cerevisiae.

Biosynthesis of polyprenols was investigated in a wild-type strain of Saccharomyces cerevisiae and a squalene synthase deficient strain auxotrophic for ergosterol. The quantitative data showed that disruption of squalene synthase gene caused a 6-fold increase in the synthesis of polyprenols in vitro in comparison with the wild-type strain. Microsomal preparation from the deleted strain only slightly reacted to the additional exogenous FPP, while that from the wild-type strain presented a 4-fold increase of polyprenol synthesis. Restoration of ergosterol synthesis, by introducing ERG9 functional allele into the deleted strain resulted in a significant lowering of polyprenol synthesis, indicating the immediate shift of the common substrate (FPP) to the sterol pathway. The role of squalene synthase in the regulation of polyprenol synthesis and 'flow diversion hypothesis' is discussed.