Squalene from presqualene diphosphate

Catalysis with [Rh2(55-mepy)4] was extended from styrene to other olefins, for which excellent results were dso obtained. By using this chiral catalyst, it has recently been possible to fix the three stereocenters in the cyclopropane ring of (+)-( R,2R,3/ )presqualene diphosphate (Structure 9), an intermediate in the biosynthesis of squalene from famesyl diphosphate [25]. 

The second step in the squalene biosynthesis is the reductive rearrangement of presqualene diphosphate (36a) to squalene. Initial diphosphate abstraction formally gives a primary cyclopropylcarbinyl catimi 37a that rearranges via a secondary cyclobutylium intermediate 38a to the tertiary cyclopropylcarbinyl cation 39a (Scheme 87.12) [176-178]. Hydride attack from NADPH at C3 terminates the squalene biosynthesis. Evidence for the existence of the tertiary... 

Squalene synthase (EC 2.5.1.21) known as a membrane-bound enzyme condenses two molecules of famesyl diphosphate (FPP) in a stable intermediate, the presqualene diphosphate (PS) which is then reduced by NAD(P)H to form squalene (S). In spite of various hypotheses concerning the binding sites and reaction centers, the catalytic machinery for the two reactions and the mechanism(s) responsible for the sterol mediated regulation of squalene synthase (SQS), have not been elucidated. Sterol auxotrophic mutant strains (1) can be used as tools for such studies. Therefore, before going to purify SQS from plant sources (2), we have undertaken the purification and comparative characterization of squalene synthase (SQS) from three yeast strains the wild-type FLIOO, the mutant strain erglOB and the recombinant strain FK5188 pMF13. 

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