Mevalonic acid pathway from

The isoprenoid side chains of quinones are biosynthesized mainly by the mevalonic acid pathway from acetyl-CoA. Another pathway to biosynthesizing isoprenoids is the so-called non-mevalonate ronte by which isopentenyldiphosphate (IPP) is formed from glyceraldehyde 3-phosphate and pyrnvate. The key molecule is the famesyl-diphosphate (FPP) that accepts other IPP molecules to form polyprenyl diphosphates. 

It is immediately clear that Acanthomyops need not rely on dietary sources of terpenes but can synthesize citronellal and citral from either acetate or mevalonate. The higher total activity of the citronellal as compared with the citral probably reflects the natural preponderance of citronellal (ca. 90%) in the ant secretion. As the specific activities show, these results are consistent with a common biogenetic origin of both terpenes. In the mevalonic acid pathway as described from other organisms (13), the radioactive carbon of l-C14-mevalonate is lost upon formation of isopentenyl pyrophosphate. 

In pepper as in many plants, there are two sources of isoprene monomers the mevalonic acid pathway and the plastidal pool from pymvate and glyceraldehyde-3-phosphate [26], Pepper carotenoid biosynthesis uses the plastidal pathway for the isopentyl pyrophosphate monomers and the resident terpenoid synthases and transferases [27], Using the 5-carbon isoprene pool, the prenyl transferases sequentially... 

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...

Of the more than 20,000 known species of lichens, only a few have been analyzed and identified as containing biologically active secondary compounds. Most of the unique secondary metabolites that are present in lichens are derived from the polyketide pathway, with a few originating from the shikimic acid and mevalonic acid pathways (Table 1.1). Previous studies have suggested that the para-depsides are precursors to mefa-depsides, depsones, diphenyl ethers, depsidones and dibenzofurans.9,12... 

In fact, this is not correct Isoprene is not an intermediate, and the discovery of the true pathway started when acetate was, rather surprisingly, found to be the original precursor for all terpenes. The key intermediate is mevalonic acid, formed from three acetate units and usually isolated as its lactone. 

At present, there is no doubt about the biosynthesis of ABA by the carotenoid pathway via the MEP pathway in plants. If ABA is biosynthesized by the direct pathway, the first cyclized intermediate will be ionylide-neethanol, having a hydroxyl group at C-l derived from farnesol however, ionylideneethanol has not been found in plants, so the direct pathway is not involved in ABA biosynthesis. The mevalonic acid pathway may also be excluded because almost no 13C label was incorporated into the carbons, which would be labeled in the mevalonic acid pathway in a feeding experiment with [l-13C]-D-glucose.640... 

In contrast to plants, it has been shown that fungi biosynthesize ABA via direct pathways from IDP supplied by the mevalonic acid pathway. B. cinerea and Cercospora pini-densiflorae fed with [l-13C]-D-glucose biosynthesized ABA, C-2, C-4, C-6, C-l, C-3, C-5, C-l, C-8, and C-9 of which were labeled with 13C, being coincident with the biosynthesis of IDP by the mevalonic acid pathway (Figure 2 7).640 Fungi produce ABA-related compounds, which are converted to ABA in feeding experiments. l, 4 -tr r-Diol (3) of ABA was found... 

The basic unit in the biosynthesis of terpenes is the isoprene molecule, isopren-fenylpyrophosphate formed from acetate in the mevalonic acid pathway, which can self-condense in various ways usually head to tail , less frequently, tail to tail or head to head . 

Figure 29. Relationships h een the carbon positions in isopentenyl pyrophosphate and their sources. In the mevalonic-acid pathway, all five caibon positions in isopentenyl pyrophosphate derive from acetate and, in turn from the C-1 + C-6 and C-2 + C5 positions of glucose. In the methyierythritol-phosphate pathway, one carbon derives from the C-3 + C-4 position in glucose. Moreover, the mapping of positions from preciu ors into products of the two pathways differs sharply, as indicated by stmctures of acyclic and steroidal carbon skeletons based on the MVA (a, c) and MEP pathways (b, d).

The existence of morphologically identical plants which possess oils that have differing chemical compositions is not a new concept. In fact, the existence of infraspecific differences is widespread in the Labiatae and Compositae families, but it is not limited to them. A lew years ago Lawrence (2) showed that Ocimnm basilicum L. can contain oils that possess a variety of compositions. It was also found (hat oils contained constituents that were biosynthesized either via the shikimic acid pathway, or the mevalonic acid pathway, or both (Figure 11). A summary of the data obtained during the analysis of more than 200 separate O. basilicum plants revealed that they possessed oils that, not only contained components from single pathways or dual pathways, but also within these groupings a wide quantitative variation of constituents was also observed. A summary of these data can be seen in Tables X and XI. 

Iridoids are synthesised through the mevalonic acid pathway and are technically known as cyclopentan-[c]-pyran monoterpenoids. They occur mainly as glycosides althongh non-glycosidic iridoids also occur— these are covered in Chapter 5. The name iridoid is derived from the common Anstralian meat ant Iridomyrex detectus, from which it was first detected in 1956 (Sticher 1977). Iridoid glycosides are derived from plants belonging to many families, most notably the Rubiaceae, Lamiaceae, Scrophulariaceae and Gentianaceae. 

Terpenoids, or terpenes, comprise one of the most important gronps of active componnds in plants with over 20 000 known strnctnres. All terpenoid strnctnres may be divided into isoprene (five-carbon) nnits containing two nnsatnrated bonds. They are synthesised from acetate via the mevalonic acid pathway. 

The mevalonic acid pathway producing IPP from acetyl CoA takes place in the cytosol of the cells. The steps include the formation of 3-hydroxy-3-methylglutaryl-CoA from three acetyl CoA, the reduction to mevalonic acid, the subsequent activation with ATP resulting in the formation of mevalonate diphosphate, and finally the decarboxylation of mevalonate diphosphate to release IPP. 

Steviol glycosides are derived from the mevalonic acid pathway. The ent-kaurene skeleton of stevioside is formed via 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway [59, 60]. High activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in chloroplasts of Stevia rebaudiana has been reported [61]. Hence, the investigators anticipated mevalonic acid (MVA) as an intermediate of steviol biosynthetic route on the basis of the fact that HMG-CoA reductase is a key enzyme of the MVA route to isopentenyl-diphosphate (IPP). 

Lichen secondary metabolites are derived from three chemical pathways acetate-polymalonate pathway, shikimic acid pathway and mevalonic acid pathway (Fig. 1.3). 

Lichens had to evolve diverse biosynthetic pathways to produce such complex arrays of secondary metabolites polyketide, shikimic acid, and mevalonic acid pathways. Most of the lichen substances are phenolic compounds. Polyketide-derived aromatic compounds, depsides, depsidones, dibenzofurans, xanthones, and naphthoquinones, are of great interest. Compounds from other pathways are esters, terpenes, steroids, terphenylquinones, and pulvinic acid (Fahselt 1994 Cohen and Towers 1995 Muller 2001 Brunauer et al. 2006, 2007 Stocker-Worgotter and Elix 2002 Johnson et al. 2011 Manojlovic et al. 2012). So, many lichens and lichen products have proved to be a source of important secondary metabolites for food and pharmaceutical industries (Huneck 1999 Oksanen 2006)... 

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