DMAPP diphosphate

The conversion of isopentenyl diphosphate (IPP) to terpenoids begins with its isomerization to dimethylallyl diphosphate, abbreviated DMAPP and formerly called dimethylallyl pyrophosphate. These two C5 building blocks then combine to give the C10 unit geranyl diphosphate (GPP). The corresponding alcohol, geraniol, is itself a fragrant terpenoid that occurs in rose oil. 

The isomerization of isopentenyl diphosphate to dimethylally diphos phate is catalyzed by JPP isomerase and occurs through a carbocation pathway Protonation of the IPP double bond by a hydrogen-bonded cysteine residue ir the enzyme gives a tertiary carbocation intermediate, which is deprotonated b a glutamate residue as base to yield DMAPP. X-ray structural studies on the enzyme show that it holds the substrate in an unusually deep, well-protectec pocket to shield the highly reactive carbocation from reaction with solvent 01 other external substances. 

Figure 27.9 Mechanism of the coupling reaction of dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP), to give geranyl diphosphate (GPP).

The biosynthesis of monoterpenes, the major components of peppermint essential oils, can be divided into four stages (Fig. 9.4). Stage 1 includes the formation of isopentenyl diphosphate (IPP) and dimethylallyl alcohol (DMAPP). In plants, two separate pathways are utilized for the synthesis of these universal C5 intermediates, with the cytosolic mevalonate pathway being responsible for the formation of sterols and certain sesquiterpenes, and the plastidial mevalonate-independent pathway being involved in the biosynthesis of isoprene, monoterpenes, certain sesquiterpenes, diterpenes, tetraterpenes, as well as the side chains of chlorophyll and plastoquinone.16 In peppermint oil gland secretory cells, however, the mevalonate pathway is blocked and the biosynthesis of monoterpenoid essential... 

Chrysanthemic acid (1) consists of ten carbons, suggesting that it is a monoterpene. The cyclopropane ring of the acid moiety is a feature of pyrethrins. Rivera et al. isolated chrysanthemyl pyrophosphate synthase (CPPase or alternatively referred to as chrysanthemyl diphosphate synthase) underlying the formation of chrysanthemyl pyrophosphate (16) containing a cyclopropane ring from two molecules of dimethylallyl pyrophosphate (15) (DMAPP) and the gene thereof [21]. They found that the reaction involves the cF-2-3 cyclopropanation of DMAPPs in a non-head-to-tail manner. 

Ginsenosides are bios)mthesized via the isoprenoid pathway in the cytosol with mevalonic acid as the precursor for isopentenyl diphosphate (IFF) and dimethylallyl diphosphate (DMAPP), which are the two C5 starting units in the bios)mthesis of ginsenosides and other terpenoids... 

Fig. 11 Natural rubber is produced from a side branch of the ubiquitous isoprenoid pathway, with 3-hydroxy-methyl-glutaryl-CoA (HMG-CoA) as the key intermediate derived from acetyl-CoA by the general mevalonic-acid pathway. Mevalonate diphosphate decarboxylase (MPP-D) produces IPP, which is isomeiized to DMAPP by IPP isomerase (IPI). IPP is then condensed in several steps with DMAPP to produce GPP, FPP and GGPP by the action of a trani-prenyltransferase (TPT). The cA-l,4-polymeiization that yields natural rubber is catalyzed by cA-prenyltransferase (CPT), which uses the non-allylic IPP as substrate. Reprinted from [248], with permission from Elsevier...

Recently Fujiwara et al. reported on the in vitro polymerization of trans-polyisoprene using the enzymes isopentenyl diphosphate isomerase (IDI) and fra 3-isoprenyl diphosphate synthase (IDS) [271]. IDI catalyzes the interconversion of IPP and DMAPP. IDS can now catalyze the polymerization of IPP from DMAPP as outlined above for the synthesis of natural rubber, and as outlined in Fig. 13a. However, the condensation process is inhibited due to hydrophobic interaction between IDS and hydrocarbon of the longer products. The hydrophobic chain of the elongating product does not readily protrude into the aqueous phase and it tends to interact with the enzyme. To achieve an efficient in vitro synthesis, the authors used an organic-aqueous two-liquid phase system to successfully synthesize (low molecular weight) fran.y-polyisoprene (see Fig. 13b). 

This dependence on light levels and temperature is believed to be due to the mechanism of production of isoprene in the plant, which involves the enzyme isoprene synthetase and dimethylallyl diphosphate (DMAPP) as a precursor to isoprene (e.g., see Silver and Fall, 1995 and Monson et al., 1995). Either the enzyme, the formation of DMAPP, or both may be light sensitive (Wildermuth and Fall, 1996). The temperature effect has been attributed to effects on the enzyme, increasing its activity initially and then leading to irreversible denaturation (and/or possibly membrane damage) (Fall and Wildermuth, 1998). 

Terpenes, biogenetically, arise from two simple five-carbon moieties. Isoprenyl-diphosphate (IPP) and dimethylallyldiphosphate (DMAPP) serve as universal precursors for the biosynthesis of terpenes. They are biosynthesised from three acetylcoenzyme A moieties through mevalonic acid (MVA) via the so-called mevalonate pathway. About 10 years ago, the existence of a second pathway leading to IPP and DMAPP was discovered involving l-deoxy-D-xylulose-5-phos-phate (DXP) and 2C-methyl-D-erythritol-4-phosphate (MEP). This so-called non-mevalonate or deoxyxylulose phosphate pathway starts off with the condensation of glyceraldehyde phosphate and pyruvate affording DXP. Through a series of reactions as shown in Fig. 4.1, IPP and DMAPP are formed, respectively [3,7, 42, 43]. 

A C5 isoprene unit in the form of dimethylallyl diphosphate (DMAPP) may also act as an... 

Fig. 2 Biosynthetic route to terpenes. Geranyl diphosphate (5) famesyl diphosphate (6) gera-nylgeranyl diphosphate (7) (-)-limonene (8) (-)-camphene (9) taxadiene (10) casbene (II) capsidiol (12). IPP = isopentenyl diphosphate, DMAPP = dimethylallyl diphosphate...

Fig. 15.5 Some isoprenoid diphosphate carbocation intermediates involved in cholesterol biosynthesis, along with some nitrogen containing bisphosphonates, their proposed transition-state-analogues. (DMAPP = dimethylallyl diphosphate,...

---