Hopene synthase

In green plants, which contain little or no cholesterol, cydoartenol is the key intermediate in sterol biosynthesis.161-1623 As indicated in Fig. 22-6, step c, cydoartenol can be formed if the proton at C-9 is shifted (as a hydride ion) to displace the methyl group from C-8. A proton is lost from the adjacent methyl group to close the cyclopropane ring. There are still other ways in which squalene is cyclized,162/163/1633 including some that incorporate nitrogen atoms and form alkaloids.1631 One pathway leads to the hop-anoids. These triterpene derivatives function in bacterial membranes, probably much as cholesterol does in our membranes. The three-dimensional structure of a bacterial hopene synthase is known.164 1643 Like glucoamylase (Fig. 2-29) and farnesyl transferase, the enzyme has an (a,a)6-barrel structure in one domain and a somewhat similar barrel in a second domain. 

The active site lies in a large interior cavity. The properties of the hopene synthase are similar to those of oxidosqualene synthase, and it appears to function by a similar mechanism, which resembles that of Fig. 22-6 but does not depend upon 02. Hopene lacks polar groups, but these are provided in the hopanoids by a polyol side chain. One of these compounds, bacteiiohopanetetrol, may be one of the most abundant compounds on earth.160 165 166 Hopanoids appear to originate from mevalonate synthesized via the 1-deoxyxylulose pathway (Fig. 22-2). The polyol side chain is probably formed from ribose.166... 

Class 11 terpene cyclases are known for the cycUzation of di-, sester-, and triterpenoids. Prominent examples of triterpene cyclases are the human lanosterol synthase (oxidosqualene cyclase, OSC) and the squalene/hopene cyclase (SHC) firom A. acidocaldarius [1]. Both enzymes have a py-domain architecture (Fig. 87.15a). The p-domain exhibits a highly regular Oe-Oe barrel structure with six inner and six outer helices surrounding a central cavity (Fig. 87.15b) [198,199, 208]. The y-domains may have originated from the p-domains by gene duplicatimi... 

---