GGPP synthases

FPP is necessary for the synthesis of both sterols and longer chain nonsterol isoprenoids. The first committed step in sterol synthesis is catalyzed by the enzyme squalene synthesis and involves the head-to-head condensation of two FPP molecules to form squalene [15]. This is followed by cyclization steps, leading to sterol synthesis. The addition of IPP to FPP via the enzyme GGPP synthase yields the 20-carbon GGPP [16]. FPP and GGPP are substrates in the prenylation reactions catalyzed by the enzymes farnesyl transferase (FTase) and geranylgeranyl transferase (GGTase) I and II [17-20]. 

GGPP synthase Arabidopsis thaliana Scolnick and Bartley (1996) Scolnick and Bartley (1994)... 

Discovery Gerfelin was isolated from culture broth of Beauveria felina QN22047 as a compound showing inhibitory activity against human geranylger-anyl diphosphate (GGPP) synthase [1,2]. The structure was determined as 1 [2]. Methylgerfelin (2) is a synthetic derivative of 1. 

GGPP synthase Croton sublyratus GGPP synthase Sinapis alba... 

PalDS6 Ptcea abies GGPP synthase Gingko biloba... 

GGPP synthase Abies grandis — PalDS2 Picea abies... 

Fig. 1.6 Phylogenetic tree of gymnosperm and angiosperm isoprenyl diphosphate synthase sequences. The isolated Picea ahies sequences are marked other isoprcnyl diphosphate synthases sequences are listed according to the major reaction product of the recombinant protein. Abbreviations GPP synthase, geranyl diphosphate synthase FPP synthase, famesyl diphosphate synthase and GGPP synthase, geranyl geranyl diphosphate synthase large su, large subunit of protein small su, small subunit of protein.

Fig. 5.3 Carotenoid biosynthesis in maize endosperm. Compounds IPP, isopentenyl pyrophosphate FPP, famesyl pyrophosphate GGPP, geranylgeranyl pyrophosphate DMAPP, dimethallyl pyrophosphate. Carotenoid biosynthetic pathway enzymes PSY, phytoene synthase PDS, phytoene desaturase ZDS, zetacarotene desaturase ISO, carotene isomerase LCY-B, lycopene beta cyclase LCY-E, lycopene epsilon cyclase HYD-B, beta-carotene hydroxylase HYD-E, alpha-carotene hydroxylase Isonrenoid biosynthetic pathway enzymes IPPI (IPP isomerase) GGPPS (GGPP synthase). Structures are not representative of the geometrical isomer substrates (e.g. Z-phytoene is a bent structure).

Four molecules of IPP, one of which is an isomer produced by IPP isomerase (IPPI) are combined to produce the twenty-carbon isoprenoid, GGPP (geranylgeranyl pyrophosphate). This step is mediated by GGPP synthase (GGPPS). Light-induced activation of IPPI has been associated with the phytochrome-... 

It is now known that there are more than 380 kinds of natural taxane in Taxus. The biosynthesis of taxanes is generally believed to occur as follows. Farnesyl diphosphate (FPP) and isopentenyl pyrophosphate (IPP) are first catalyzed by GGPP synthase to produce geranylgeranyl-pyrophosphate (GGPP), and then taxa-4(5),ll(12)-diene is produced under the action of taxa-diene synthase. Next, taxanes are produced by the hydroxylase oxidation of the taxa-4(20),ll(12)-dien-5a-ol diterpene parent ring. The biosynthetic pathway for taxanes is illustrated in Figure 6.7. 

Subsequently, the intact incorporation of multiply H-labeled 3-geranylgeranylind ole 49b into paxilline proved that 3-geranylgeranylindole is a biosynthetic intermediate of indole-diterpenes (Figure 5.59) [256]. Thus, the proposal for the early steps of paxilline biosynthesis involves the formation of 3-geranylgeranylindole 49a catalyzed by GGPP synthase, subsequent epoxidation, and cationic cyclization to produce emindole SB. 

The recombinant production of ferruginol, which is the precursor of the anticancer com-poimds tanshinones, was achieved by using CYP76AH1 in a strain optimized for miltiradiene accmnulation and reached titers of 10.5 mg L [401]. In addition, the strain contained an artificial fusion protein of GGPP synthase and FPP synthase as well as a truncated HMGR and a fused synthetic mitiradiene-CPP synthase module (Fig. 8.14). 

Fig. 8.16 Pathways for the production of hydroxylated carotenoids in . coli. Isopentenyl pyrophosphate (IPP) and farnesyl diphosphate (FPP) are produced via internal methylerythritol phosphate (MEP) pathway and FPP synthase. CrtE GGPP synthase, CrtB phytoene synthase, CrtI phytoene dehydrogenase, LycB lycopene p-cyclase, LycE lycopene e-cyclase...

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