Formation of Dehydrosqualene Catalyzed by Squalene Synthetase in Saccharomyces cerevisiae

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When microsomal fraction of Saccharomyces cerevisiae was incubated with farnesyl pyrophosphate or presqualene pyrophosphate in the presence of Mn²⁺, 12, 13-cisdehydrosqualene (DeH₂Sq) and some related compounds were found to be formed. Incubation in the presence of NADPH gave rise to only squalene. By heat treatment of the microsomal fraction, the DeH₂Sq- and squalene-forming activities were inactivated at approximately the same rate. The elution patterns of both activities upon Sephacryl S-200 chromatography of the enzyme solubilized from the microsomal fraction with taurodeoxycholate coincided completely. These results indicate that DeH₂Sq formation in yeast is catalyzed by squalene synthetase. Divalent cation was essential for this reaction and Mn²⁺ was six times more effective than Mg^2-. DeH₂Sq formation was also observed when microsomes of pig liver were used instead of yeast microsomal fraction, suggesting that this reaction is a ubiquitous one among the eucaryotes which are capable of synthesizing sterols. Based on these observations, the mechanisms of DeH₂Sq and squalene formations are discussed.