Enzymatic Polyene Cyclisation

The enantioselective polyene cyclisation of squalene to the pentacydic hopene and hopanol ranks as one of the most complicated biochemical reactions. In a single step, nine stereogenic centres are formed. Hopene is one of 512 (2 ) possible stereoisomers. 

The cyclisation is mediated by squalene-hopene cyclase from prokaryotic species, and is analogous in certain aspects to the squalene oxide - lanosterol cyclase from eukaryotic sources. [257] 

0 Hopanoids are important components of the bacterial cell wall.They may be found today in large quantities in up to 500 million years old oil shale estimates go as high as 10 tonnes.Therefore, in terms of quantity, hopanoids represent, next to cellulose, the most abundant organic materials on Earth. [256] 

In 1997, Georg E. Schulz in Freiburg succeeded in determining the structure of the membrane-bound squalene-hopene cyclase from the thermophilic microorganism Alicyclobacillus acidocaldar ms (Fig. 3.53 and Fig. 3.54). [258] The enzyme consists of two domains of approximately equal size. Between the two is a cavity with a volume of 1200 A, which contains the active site this is accessible through a non-polar channel in domain 2 (Fig. 3.55). 

Squalene is bound into the active site in a chair-chair conformation. [259] The cyclisation begins with a protonation at C-3 of the future hopene by aspartic acid D376. Carbocation n-interactions with various aromatic amino acids, such as tyrosine, phenylalanine and tryptophan, stabilise the cationic intermediates, until eventually deprotonation produces hopene and hydroxylation gives hopa-nol (Fig. 3.56). 

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