Polyprenyl synthases

Terpenes are formed by coupling double-bond isomers of the same momoner, isopentenyl pyrophosphate (IPP), with loss of a pyrophosphate ion (15, 16). Three such coupling reactions join four IPPs, each with hve carbon atoms, to make geranylgeranyl-pyrophosphate, the C2o-precursor of diterpenes such as taxol (Fig. 3). Linear terpene precursors, which differ only in the number of IPP units joined, can be assembled by a few polyprenyl synthase enzymes, as the monomers are identical and the only variable is how many monomers to link together. In subsequent steps, these linear polyenes undergo cation-induced cyclizations to create the starting frameworks for terpenes and their derivatives. 

Streptomyces avermitilis, a bacterium with a completely sequenced genome (18, 19), has three times as many predicted glycosyltransferases than predicted polyprenyl synthases. 

Other Claisen condensations are involved in synthesis of fatty acids and polyketides217 (Chapter 21) and in formation of 3-hydroxy-3-methylglutaryl-CoA, the precursor to the polyprenyl family of compounds (Chapter 22). In these cases the acetyl group of acetyl-CoA is transferred by a simple displacement mechanism onto an -SH group at the active site of the synthase to form an acetyl-enzyme.218 219 The acetyl-enzyme is the actual reactant in step b of Eq. 17-5 where this reaction, as well as that of HMG-CoA lyase, is illustrated. 

Figure 22-1 Outline of biosynthetic pathways for polyprenyl compounds. Steps e,f, and g and many subsequent steps are catalyzed by isoprenyl diphosphate synthases.

The 5-epi-aristoIochene synthase of tobacco makes the 5-epimer of aristolochene (Fig. 22-4). It binds the diphosphate group within a central cavity using two Mg2+ ions held by carboxylates, some of which are in the DDXXD sequence found also in polyprenyl diphosphate synthases. The enzyme active sites of both the epi-aristolochene synthase and a pentale-nene synthase from Streptomyces96 are rich in polar groups that form hydrogen-bonded networks and which participate in proton abstraction and donation during the rearrangement reactions that must occur. 

Ognra, K., Koyama, T, and Sagami, H. (1997). Polyprenyl diphosphate synthases. Subcell Biochem 28 57-87. 

Benzophenone synthase (BPS) and biphenyl synthase (BIS) catalyze the formation of the same linear tetraketide from benzoyl-CoA and three molecules of malonyl-CoA. However, BPS cyclizes this intermediate via intramolecular C6-+C1 Claisen condensation, whereas BIS uses intramolecular C2— C7 aldol condensation. Benzophenone derivatives include polyprenylated polycyclic compounds with hi pharmaceutical potential. Biphenyl derivatives are the phytoalexins of the economically important Maloideae. 

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