Diterpene synthases

Recently, a key player in the ginkgolide biosynthesis has been isolated and characterized A cDNA that encodes G. biloba levopimaradiene synthase, a diterpene synthase involved in ginkgolide biosynthesis, was isolated and characterized. Similarly, a new geranylgeranyl diphosphate synthase gene from G. biloba, was characterized. ... 

The prenyl diphosphates, GPP, FPP and GGPP, are the central intermediates of terpenoid bios)mthesis. Under the catalysis of monoterpene, sesquiterpene and diterpene synthases, respectively, these substances are transformed into... 

Steele, C.L., Katoh, S., Bohlmann, J. and Croteau, R. (1998b) Regulation of oleoresinosis in grand fir Abies grandis) differential transcriptional control of monoterpene, sesquiterpene and diterpene synthase genes in response to wounding. Plant Physiol, 116,1497-504. 

For instance, terpene cyclases are known to catalyze the conversion of oligomeric isoprenoid pyrophosphate substrates to polycyclic hydrocarbon products. Sequence comparisons of terpene cyclases with different known specificity can allow them to be classified into monoterpene, sesquiterpene, and diterpene synthases, which utilize the 10-carbon substrate geranyl pyrophosphate, the 15-carbon substrate famesyl pyrophosphate, and the 20-carbon substrate geranyl-geranyl pyrophosphate, respectively, on the basis of sequence criteria. 

Fig. 2.3 Biosynthetic pathway scheme for diterpene resin acids. Di-TPS is diterpene synthase P450 is cytochrome P450 dependent monooxygenase.

A huge varity of natural diterpenes, such as sdareol, derives from cyclisation reactions of geranylgeranyl diphosphate, catalyzed by diterpene synthases. These cydisation reactions can be initiated either by activation of the diphosphate moiety or by protonation of the terminal double bond. However, in the biosynthesis of many polycydic diterpenes, both types of activation are applied in two successive enzymatic reactions. In the case of the biosynthesis of sdareol in clary sage, and this is in contrast to previous biochemical experiments, two distinct synthases are involved the (13 )-8a-hydroxylabden- 15-yl diphosphate synthase (SsLPS) and the sdareol synthase (SsScS). [215]... 

Terpene synthases catalyze the first committed steps in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes. An overview is presented of the enzymology and mechanism of these terpene synthases, and their molecular cloning, expression, and sequence analysis. Detailed structural and functional evaluation of four representative monoterpene, sesquiterpene, and diterpene synthases is also presented. 

Because of the striking similarities in properties, mechanisms and primary structures between the plant monoterpene, sesquiterpene, and diterpene synthases [21], the recent crystallization and X-ray diffraction analysis of 5-epi-aristolochene synthase (Nt-EAS) [62] is of central importance in providing the first three-dimensional model with which fundamental and common structural themes may be proposed. This model provides a convenient starting point for discussing general structure/function relationships of all terpene cyclases. 

Monofunctional type II diterpene synthases from plants such as the cnf-copalyl diphosphate synthase from A. thaliana exhibit an apy-modular structure [201]. In this type of enzymes, the p-domain contains the conserved DXDD motif, but no DDXXD motif is present within the a-domain which coincides with the lack of... 

The immense diversity of terpene metabolites known today is especially due to the large terpene synthase (TPS) gene family evolution and the versatility of the enzymes encoded by it. Most gymnosperm terpene synthases form a different family from those in angiosperms. However, phylogenetic analyses support the fact that all plant TPS have evolved from an ancestral diterpene synthase implicated with primary metabolism [4]. 

The diterpene synthase copalyl diphosphate synthase (CDP) is one of the most studied type B synthases. It forms the bicycUc intermediate (-)-copalyl pyrophosphate ((-)-CPP) or its diastereomer (+)-copalyl pyrophosphate ((+)-CPP) from GGPP. Several CDPs are expressed in rice OsCycl forms (+)-CPP, while OsCyc2 and OsCPSl form (-)-CPPs. OsCPSl is believed to be involved in gibberellin biosynthesis and OsCyc2 in diterpene phytoalexin biosynthesis [31],... 

The diterpene taxol from Pacific yew is one of the most powerful anticancer agents in therapeutic use today. In a series of seminal discoveries, the group of Croteau has dissected the pathway to this complex molecule at the enzymatic and molecular genetic levels, leading to recent success in partial reconstmction of the pathway in yeast [33]. The diterpene synthase taxadiene synthase catalyzes the cyclization of GGPP as the first committed step in taxol formation [34]. 

Oxidosqualene cyclases (OSCs) or triter-pene synthases convert oxidosqualene to one or more cyclic triterpene alcohols which are the precursors of sterols, steroids and saponins [36]. The reaction catalyzed is mechanistically similar to those of monoterpene, sesqniterpene and diterpene synthases, but the enzymes are phylo-genetically distinct [37]. 

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