Kaurene synthetase

The mode of action of CCC is attributed to the inhibition of tf kaurene synthetase A, the enzyme that drives the biosynthesis of geranylgeranylpyrophosphate by copalyl pyrophosphate to /-kaurene. The compound is registered in Europe to control lodging and is registered with the EPA. 

Figure 8. The ent-kaurene synthetase system and the d5 lesion of maize, Zea mays. Apparently the ds lesion favors the loss of the proton from carbon-15 rather than from carbon-17 as is the case for normal maize. Compounds in parentheses are hypothetical intermediates. The GA s identified by GC-MS were obtained from young maize tassels (57).

Simcox, P.D., Dennis, D.T., West, C.A. "Kaurene synthetase from plastids of developing plant tissues." Biochem. Bio-phys. Res. Commun., 1975 > 66, 166-172. 

Sun, T.-P. and Kamiya, Y. (1994) The Arabidopsis GAl locus encodes the cyclase ent-kaurene synthetase A of gibberellin biosynthesis. Plant Cell, 6, 1509-18. 

In a biogenetically patterned synthesis, the cyclization of epoxygeranylgeraniol with boron trifluoride etherate has been shown to afford the compounds (103) and the pimaradienols (104). The cyclization of epoxygeranylgeranyl pyrophosphate by kaurene synthetase affords the epimeric 3-hydroxykaurenes. A cyclization of olefinic jS-keto-esters (105) to the bicyclic compound (106) has formedthe basis of a novel synthesis of A -podocarpen-13-one (107), a compound which is an intermediate in several diterpenoid total syntheses. Synthetic approaches to the... 

The kaurene synthetase from Echinocystsis macrocarpa (wild cucumber) seed is able to cyclize both R- and 5-enantiomers of 14,15-oxidogeranylgeranyl pyrophosphate to give 3a- and 3/3-hydroxykaurene respectively in good yields. The degree of flexibility of substrate revealed by the diterpenoid cyclase makes more plausible previous proposals that naturally occurring axially hydroxylated terpenoids might arise by direct cyclization of appropriate epoxide precursors. 

The dwarf-5 mutant blocks the cyclization of CPP to c /-kaurene [12] (Fig. 6). This early step in the pathway is catalyzed by the B activity of /-kaurene synthetase... 

Some examples of this group of inhibitors are shown in Fig. 1. They are characterized by the presence of a permanent positive charge or a tertiary N-atom which would be positively charged at physiological pH. AMO-1618, Phosphon D and several others were shown to inhibit activity A, but not activity B, of e /-kaurene synthetase from F. moniliforme[ 5] and M. macrocarpus [ 1]. 

Fig. 1. Structures of some inhibitors of activity A of ew/-kaurene synthetase...

In common with the e /-kaurene synthetase inhibitors, KOls may also affect phytosterol biosynthesis. Indeed, most of these compounds arose from fungicide screening programmes where the principal requirement is for inhibition of lano-sterol or 24-methylenedihydrolanosterol 14a-demethylase [28]. The equivalent enzyme in phytosterol biosynthesis, obtusifoliol 14a-demethylase, has been extracted from maize embryos and shown to be a cytochrome P-450 monooxygenase [40], which is inhibited more strongly by certain triazole fungicides than by related growth retardants [44]. 

AMO 1618 (Figure 4.9), an inhibitor of squalene cyclization and kaurene synthetase, is also an inhibitor of lycopene cyclization when used at high concentrations with the Aphanocapsa cell-free system. ... 

Recently, EPTC has been shown to inhibit the conversion of acetate and pyruvate to acetyl-CoA. However, this cannot directly explain the inhibition of enf-kaurene synthesis from MVA. It seems likely that the thiocarbamate effect on gibberellin biosynthesis is a secondary target. This was the conclusion from a study with diallate, which inhibited enf-kaurene synthetase only at high concentrations. Gibberellins may have a role in... 

Fall, R. R., and C. A. West Purification and Properties of Kaurene Synthetase from Fusarium moniliforme. J. Biol. Chem. 246, 6913 (1971). 

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