Famesyl diphosphate synthase

Lee, PC. et al., Directed evolution of Esherichia coli famesyl diphosphate synthase (IspA) reveals novel structural determinants of chain length specihcity, Metab. Eng. 7, 18, 2005. 

Cervantes-Cervantes, M. et al., Maize cDNAs expressed in endosperm encode functional famesyl diphosphate synthase with geranylgeranyl diphosphate synthase activity, Plant Physiol. 220, 2006. 

Ohnuma S, Narita K, Nakazawa T, Ishida C, Takeuchi Y, Ohto C, Nishino T (1996) A role of the amino acid residue located on the fifth position before the first aspartate-rich motif of famesyl diphosphate synthase on determination of the final product. J Biol Chem 271 30748-30754... 

AdiwUaga, K. and Kush, A. (1996) Cloning and characterization of cDNA encoding famesyl diphosphate synthase from rubber tree (Hevea brasiliensis). Plant Mol. Biol., 30,935- 6. 

Pan, Z.Q., Herickhoff, L. and Backhaus, R.A. (1996) Cloning, characterization and heterologous expression of cDNAs for famesyl diphosphate synthase from the guayule rubber plant reveals that this prenyltransferase occurs in rubber particles. Arch. Biochem. Biophys., 332, 196-204. 

Ramosvaldivia, A.C., Vanderheijden, R. and Verpoorte, R. (1997a) Elicitor-mediated induction of anthraquinone biosynthesis and regulation of isopentenyl diphosphate isomerase and famesyl diphosphate synthase activities in cell suspension cultures of Cinchona robusta How. Planta, 203, 155-61. 

Sanmiya, K., Iwasaki, T., Matsuoka, M., Miyao, M. and Yamamoto, N. (1997) Cloning of a cDNA that encodes famesyl diphosphate synthase and the blue-light-induced expression of the corresponding gene in the leaves of rice plants. Biochim. Biophys. Acta Gene Struct. Expr., 1350, 240-6. 

Song, L. and Poulter, C.D. (1994) Yeast famesyl-diphosphate synthase site-directed mutagenesis of residues in highly conserved prenyltransferase domains I and II. Proc. Natl. Acad. Sci. USA, 91, 3044-8. 

Another study with glandular trichomes from Ocimun basilicum, revealed that relative levels of GPPS and FPPS (famesyl diphosphate synthase) activities did not correlate with the total amount of terpenes produced nonetheless, it showed some correlation with the ratio monoterpene/sequiterpene [324]. 

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.

THOLL, D., CROTEAU, R., GERSHENZON, J., Partial purification and characterization of the short-chain prenyltransferases, geranyl diphosphate synthase and famesyl diphosphate synthase, from Abies grandis (Grand fir).. Arch. Biochem. Biophys., 2001,386, 233-242. 

Prenyltransferase activities have been studied in C. roseus both at the enzyme level and at the product level. Biosynthetic capabilities were investigated by incubating [1- C]IPP with aliquots of cell-free homogenates prepared from P. aphanidermatum treated and untreated suspension-cultured cells of C. roseus. After elicitation, the total incorporation of IPP into prenyl lipids was decreased, in particular into squalene. But the incorporation of IPP into some (as yet unidentified) compounds was increased (99). The prenyltransferases and subsequent enzyme activities are relatively easily extracted and remain complexed so that the product of one enzyme can be used as a substrate for the next enzyme. With an assay for these enzymes as described in detail in Threlfall and Whitehead (101), about a dozen enzyme activities could be detected in series using cell-free preparations of elicited Tabemaemontana divaricata cells (27). In the elicited C. roseus cells, the activities of IPP isomerase, famesyl diphosphate synthase, squalene synthase, squalene-2,3-epoxidase (and probably also a squalene-2,3-epoxide cyclase) were thus detected. Compared with the control nontreated cells, squalene production seemed to be reduced particularly (99). 

In the case of natural rubber from Hevea brasiliensis, which is almost entirely made of cis-isoprene units, it could be assumed that ci5-prenyltransferase is exclusively involved in phase 2. Unfortunately it is more complex. Authors agree on phase 1, which is traws -condensation catalyzed by a cytosolic soluble trans-prenyl transferase" Famesyl diphosphate synthase has been cloned from rubber latex.The most probable prenyldiphosphate used as a primer for phase 2 is famesyl-PP (15) or geranylgeranyl-PP (16)." " Phase 2 is catalyzed by a still not clearly identified rubber transferase system. Different proteins have been... 

The biosynthesis of rubber may be divided into three steps (1) initiation, which requires an allylic diphosphate molecule, (2) elongation, in which IPP units are added to a Z-l,4-polyisoprene chain, and (3) termination, in which the polymer is released from the rubber transferase enzyme (Cornish, 1993). In plants, the elongation of Z-l,4-polyiso-prene (natural rubber) requires a small -allylic diphosphate initiator (less than or equal to C20). Famesyl pyrophosphate (FPP) is an effective initiator of polyisoprene biosynthesis (Light et al, 1989) further, because only one molecule of FPP is needed for each molecule of rubber formed, small traces of this substance that are inadvertently present complicate biosynthetic studies. The E-allylic diphosphates are hydrophilic cytosolic compounds, whereas Z-l,4-polyisoprene is hydrophobic and compartmentalized in subcellular rubber particles. A soluble E-prenyl transferase from the latex of Hevea brasiliensis serves as a famesyl diphosphate synthase and plays no direct role in elongation of Z-l,4-polyisoprene (Cornish, 1993). Because the hydro-phobic rubber molecule is produced inside a rubber particle but is formed from hydrophilic precursors from the cytoplasm, the polymerization reaction must take place at the particle surface. 

In the biosynthesis of steroids lanosterol and cycloartenol, the building blocks DMAPP and IPP are first joined through famesyl diphosphate synthase to form geranyl pyrophosphate (GPP) and then to form FPP, presqualene pyrophosphate, squalene, and (S)-squalene-2,3-epoxide by corresponding enzymes, sequentially. The product (S)-squalene-2,3-epoxide is used to synthesize the sterols lanosterol (in animals) and cycloartenol (in plants) by lanosterol synthase and cycloartenol synthase, respectively [3]. Further, lanosterol and cycloartenol are converted into other steroids through steroidogenesis. 

Famesyl diphosphate (FPP) is the starting molecule for the committed step in sesquiterpene biosynthesis, so artemisinin is synthesized from FPP via the mevalonate pathway in the cytosol (Fig. 89.15). A rational approach has enhanced artemisinin yields by the overexpression of famesyl diphosphate synthase... 

Chen DH, Liu CJ, Ye HC, Li GF, Liu BY, Meng YL, Chen XY (1999) Ri-mediated transformation of Artemisia annua with a recombinant famesyl diphosphate synthase gene for artemisinin production. Plant Cell Tissue Organ Cult 57 157-162... 

Han J, Liu B, Ye H et al (2006) Effects of overexpression of the endogenous famesyl diphosphate synthase on the artemisinin content in Artemisia annua L. J Integr Plant Biol 48 482 87... 

Matsushita Y, Kang W, Charlwood BV (1996) Qoning and analysis of a cDNA encoding famesyl diphosphate synthase from Artemisia annua. Gene 172 207-209... 

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