Farnesyl diphosphate, biosynthesis

Figure 27.12 An overview of steroid biosynthesis from farnesyl diphosphate.

Fig. 11.3 Biosynthesis of the homoterpenes (a) DMNT (4,8-dimethyl-l,3,7-nonatriene) and (b) TMTT (4,8,12-trimethyltrideca-l,3,7,l 1-tetraene). (b) Two putative reaction mechanisms for the conversion of (ii,Zi)-geranyUinalool to TMTT catalyzed by a P450 enzyme activity are shown. FPP, farnesyl diphosphate GGPP, geranylgeranyl diphosphate...

By far the most impressive example of electrophilic addition in natural prodnct formation is in the biosynthesis of steroids. The snbstrate sqnalene oxide is cyclized to lanosterol in a process catalysed by a single enzyme. Lanosterol is then converted into the primary animal-steroid cholesterol. Sqnalene oxide comes from sqnalene, which is itself formed throngh a combination of two molecules of farnesyl diphosphate. 

Prenylation, the key step in terpene biosynthesis, is catalyzed by prenyltransferases. These enzymes are responsible for the condensation of isopentenyl pyrophosphate (IPP) with an allyl pyrophosphate, thus yielding isoprenoids. Numerous studies have been performed with fluorinated substrates in order to determine the mechanism of the reactions that involve these enzymes prenyltransferases, farnesyl diphosphate synthase (FDPSase), famesyltransferase (PFTase), and IPP isomerase. These studies are based on the potential ability of fluorine atoms to destabilize cationic intermediates, and then slow down S l type processes in these reactions. 

The chiral hydrocarbon germacrene D is a widely spread plant constituent and is considered to be an important intermediate in the biosynthesis of many sesquiterpenes. Schmidt et al. [19, 20] have shown that the plant Solidago canadensis generates both optical antipodes of this compound by enzymatic cyclisation of farnesyl diphosphate using two different enantiospecific synthases. As to be seen in Fig. 17.5, the enantiomeric ratio of germacrene D in Solidago canadensis can vary from individual to individual [21]. 

ATP -h trans-farnesyl diphosphate <1> (<1> possibly involved in control of biosynthesis of terpenoids in Gibberella fujikuroi [2]) (Reversibility <1> [2]) [2]... 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

Figure 27 Four possible pathways for ABA biosynthesis. Open and closed circles show the 13C label from [1-13C]-d-glucose in the mevaloic acid pathway and the MEP pathway, respectively. DAP, dihydroxyacetone phosphate DXP, 1-deoxy-xylulose-5-phosphate FDP, farnesyl diphosphate GAP, glyceraldehyde-3-phosphate GGDP, geranylgeranyl diphosphate HMG-CoA, 3-hydroxy-3-methylglutaryl CoA IDP, isopentenyl diphosphate MEP, 2-C-methyl-D-erythritol-4-phosphate.

The genetic engineering of qinghao (4. annua) has also been paid great attention recently some preliminary results about the early stage of qinghaosu biosynthesis have been reported. For example, amorpha-4,11-diene synthase, an enzyme responsible for the cyclization of farnesyl diphosphate into ring sesquiterpene, has been expressed in Escherichia coli and production of amorpha-4,11-diene (122) was identified. °... 

Figure 1 Schematic overview of the biosynthesis of the monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. Representatives of these classes with biological relevance are shown. Enzymatic steps are indicated in italics DMADP, dimethylallyl diphosphate CDP, geranyl diphosphate GGDP, geranylgeranyl diphosphate FDP, farnesyl diphosphate IDP, isopentenyl diphosphate.

Diterpenoids are derived biosynthetically from geranylgeranyl diphosphate (GGPP), which is itself biosynthesized by reaction of farnesyl diphosphate with isopentenyl diphosphate. Show the structure of GGPP, and propose a mechanism for its biosynthesis from FPP and IPP. 

Propose a mechanism for the biosynthesis of the sesquiterpene trichodiene from farnesyl diphosphate. The process involves cyclization to give an intermediate secondary carbocation, followed by several carbocation rearrangements. 

The biosynthesis of the illudins from C-acetates and variously stereo-specifically labelled mevalonates has been studied. The results are in accord with the cyclization of farnesyl diphosphate set out in 5.59 5.65. 

A more efficient process to paclitaxel involves fermentation [69-71]. The biosynthesis starts from isoprenyl diphosphate and farnesyl diphosphate (Scheme 8.17). To achieve a high titer of paclitaxel production, cell cultures from various species of Taxus were investigated. For example, methyl jasmonate was able to enhance paclitaxel production to 55 mg I 1 per week in a cell suspension culture. The plant... 

Studies of the biosynthesis of heptelidic acid indicate that cis, trans-farnesyl diphosphate can act as the biosynthetic precursor (Scheme 20). Ring closure is initiated by a stereospecific 1, 3-hydride shift during which the methyls of the isopropyl group retain their identity [194, 195, 198]. The remaining sequence as shown in the Scheme also includes a rationalization for the generation of gliocladic acid (141) and the hydroxy acid (139). It should be mentioned that the evidence for structure 139 is lacking [206], but it appears to be an acceptable structure insofar as it is... 

Biosynthesis By cyclization of farnesyl diphosphate, rearrangement, and subsequent elimination. 

Biosynthesis Farnesyl diphosphate is converted to trails- fi-hergamotene by cyclization of an intermediate bisabolyl cation. Oxidative ring opening followed by three specific oxidation reactions leads to O.. ... 

The biosynthesis of steroids proceeds via farnesyl diphosphate and squalene (Fig. 6.7). It is fascinating that Nature applies here the same principles as they are also found in the biosynthesis of carotenoids and pyrethroids. 

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. 

Figure 7.26 Biosynthetic pathway of diazepinomicin biosynthesis of farnesyl-diphosphate and the final step.

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