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 auxo trophic for ergosterol, The quantitative data showed that disruption o f squalene synthase gene caused a 6-fold increase in the synthesis of polyprenols in vitro in comparison with the wild-type strain, Microsom al preparation from the deleted strain only slightly reacted to the ad ditional 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 stra in resulted in a significant lowering of polyprenol synthesis, indicat ing the immediate shift of the common substrate (FPP) to the sterol pa thway. The role of squalene synthase in the regulation of polyprenol s ynthesis and 'flow diversion hypothesis' is discussed. (C) 1998 Federa tion of European Biochemical Societies.