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

AbstractBiosynthesis 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