FPP synthases

Mevalonate kinase Phosphomevalonate kinase Mevalonate PP decarboxylase GPP synthase IPP isomerase FPP synthase Squalene synthase... 

GPP synthase Citrus sinensis GPP synthase Quercus robur GPP synthase Arabidopsis thaliana PalDSS Picea abies PPP synthase Arabidopsis thaliana FPP synthase Musa acuminata FPP synthase Artemisia annua FPP synthase Gingko biloba... 

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.

FPP) synthase were partially purified from C. roseus suspension-cultured cells (98). 

Most evidence supports synthesis of sesquiterpenes in the cytosol/microsomal compartment of plant cells (Threlfall and Whitehead, 1991). The endoplasmic reticulum appears to be the site of FPP synthase (prenyltransferase) and sesqui-... 

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...

In contrast to the head-to-tail connected polyisoprenoids, squalene (C30) and phytoene (C40) arise from a head-to-head condensation of two molecules FPP or GGPP, respectively. The squalene synthase requires divalent metal ions Mn " as well as an NADPH cofactor. Superimposition of the crystal structure of human squalene synthase with avian FPP synthase reveals a close structural homology, although the sequence identity in the superimposed parts is low [164]. Due to their distinct functionality, the highly a-helical squalene synthases (Fig. 87.11) have been designated an own type of head-to-head prenyltransferases termed E-class. The highly conserved DDXXD motifs in a-prenyltransferases are altered to DTLED and DYLED motifs in the human squalene synthase. 

In all living organisms, famesyl synthases convert isopentenyl pyrophosphate (IPP) into famesyl pyrophosphate (FPP) (77), the precursor of all sesquiterpene structures. The enzyme generating FPP, FPP synthase, has been extensively studied, and it was shown that the E,E conformation of FPP is the predominant product of famesyl synthases and generally is the substrate for sesquiterpene synthases in eukaryotes [22]. 

Figure 3.8 Schematic representation of the active site of FPP synthase. The large hydrophobic residue...

Natural rubber can be regarded as a 1,4-addition polymer of isoprene. The basic building block of five carbons for the polymerization is 3-isopentenyIpyro-phosphate (3-IPP). The first reaction is an enzymatic isomerization of the olefin of 3-IPP to 2-isopentenylpyrophosphate (2-IPP). The carbon-carbon bond formation between these two pyrophosphates initiates the polymerization in which the pyrophosphate group acts as a leaving group. The isoprene units of natural rubber are all linked in a head-to-tail fashion and all of the double bonds have a cis-structure. The stereocontrol of the formation of the cis-unit is achieved by the function of the elongation factor which combines with the famesyl pyrophosphate (FPP) synthase [16]. 

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