Mevalonic acid derivatives

In addition to polyketides and mevalonic acid-derived species, acetyl-CoA moves through the TCA (or the citric acid cycle, or the Krebs cycle), a cycle (which by dehnition cannot have a beginning or end) that serves to produce many useful fragments as well as to effect the complete oxidation of pyruvic acid. As shown in Scheme 11.89, as acetyl-CoA enters the already turning cycle, an addition to the carbonyl group of oxaloacetate occurs (citrate synthase, EC 2.3.3.1) to produce citrate. In the addition process, the methyl group of the acetyl-CoA becomes the pw-S carbon in citrate. 

Introduction of Nitrogen into a Terpenoid Skeleton. The acetate-derived fragments (35) mevalonic acid (30), which yields isopentenyl pyrophosphate (31) and its isomer, 3,3-dimethyl ally pyrophosphate (32) a dimeric C -fragment, geranyl pyrophosphate (33), which gives rise to the iridoid loganin (34) and the trimer famesyl pyrophosphate (35), which is also considered the precursor to C q steroids, have already been mentioned (see Table 3... 

The principal steps in the mechanism of polyisoprene formation in plants are known and should help to improve the natural production of hydrocarbons. Mevalonic acid, a key intermediate derived from plant carbohydrate via acetylcoen2yme A, is transformed into isopentenyl pyrophosphate (IPP) via phosphorylation, dehydration, and decarboxylation (see Alkaloids). IPP then rearranges to dimethylaHyl pyrophosphate (DMAPP). DMAPP and... 

A considerable number of mycotoxins that show high toxicity to vertebrates and/ or invertebrates are produced by organisms associated with crop plants (Flannigan 1991). There are many known cases of human poisoning caused by such compounds. There are three broad categories of mycotoxins represented here, based on the structures of the intermediates from which these secondary metabolites are derived. They are (1) compounds derived from polyketides, (2) terpenes derived from mevalonic acid, and (3) cyclic peptides and derivatives thereof. 

Since carotenoids are isoprenoids, they share a common early pathway with other biologically important isoprenoids such as sterols, gibberellins, phytol and the terpenoid quinones (Fig. 13.3). In all cases, these compounds are derived from the C5 isoprenoid, isopentenyl diphosphate (IPP). Until a few years ago it was believed that a single pathway from the Cg precursor mevalonic acid (MVA) formed IPP, which itself was synthesised from hydroxymethylglutaryl coenzyme A (HMG CoA) by the action of HMG... 

Another example of a nudibranch, which probably modifies dietary metabolites to obtain more effective allomones, is seen in Aldisa cooperi (= A. sanguinea cooperi) [155]. It elaborates two fish antifeedant bile acids (104,105) that are absent in its prey, the sponge Anthoarcuata graceae, where the main steroid is 4-cholesten-3-one (106). Biosynthetic experiments starting from both labelled mevalonic acid and labelled 4-eholesten-3-one would definitely clarify, whether, the two allomones (104-105) are biosynthetized de novo by the mollusc, or if they are derived from a food source. 

Fig. 2 Two possible biosynthetic pathways to pyrethrolone. The [l-13C]D-glucose-derived 13C labels that occur in the mevalonic acid and 2-C-methyl-D-erythritol 4-phosphate (13) pathways are colored in red and green, respectively. The phosphate moiety is indicated as P ...

It is well established that the iridoids are derived from two units of mevalonic acid (97), which itself is derived from acetyl-CoA. Mevalonate is also known to be a metabolic product of leucine (172), and the latter is a precursor of the monoterpene linalool (173). Wigfield and Wen (174) pursued the incorporation of leucine into the monoterpene unit in both vindoline (3) and catharanthine (4), where levels of 0.07 and 0.02%, respectively, were found, irrespective of the amount of precursor fed. This was important because, although initial results were obtained with [2- C] leucine, the specificity of incorporation was determined with 2- C-la-beled precursor. Two carbons in vindoline (3), C-8 and C-24, were en-... 

The route of formation of the carbazole nucleus is still far from understood, and has been variously considered to arise from 3-prenylquinolone via a pathway involving shikimic acid (394) and mevalonic acid (MVA) (400) (Scheme 3.1) (1,112,362-366), anthranilic acid (397) and prephenic acid (404) via a pathway involving shikimic acid (394) (Scheme 3.2) (367), and also tryptophan (408) involving the mevalonate (400) pathway (Scheme 3.3) (133). All of these pathways lack experimental proof. However, based on the occurrence of the diverse carbazole alkaloids derived from anthranilic acid (397) in the family Rutaceae, the pathway... 

Alkaloid biosynthesis needs the substrate. Substrates are derivatives of the secondary metabolism building blocks the acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid and 1-deoxyxylulose 5-phosphate (Figure 21). The synthesis of alkaloids starts from the acetate, shikimate, mevalonate and deoxyxylulose pathways. The acetyl coenzyme A pathway (acetate pathway) is the source of some alkaloids and their precursors (e.g., piperidine alkaloids or anthraniUc acid as aromatized CoA ester (antraniloyl-CoA)). Shikimic acid is a product of the glycolytic and pentose phosphate pathways, a construction facilitated by parts of phosphoenolpyruvate and erythrose 4-phosphate (Figure 21). The shikimic acid pathway is the source of such alkaloids as quinazoline, quinoline and acridine. 

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...

Until 1993, all terpenes were considered to be derived from the classical acetate/mevalonate pathway involving the condensation of three units of acetyl CoA to 3-hydroxy-3-methylglutaryl CoA, reduction of this intermediate to mevalonic acid and the conversion of the latter to the essential, biological isoprenoid unit, isopentenyl diphosphate (IPP) [17,18,15]. Recently, a totally different IPP biosynthesis was found to operate in certain eubacteria, green algae and higher plants. In this new pathway glyceradehyde-3-phosphate (GAP) and pyruvate are precursurs of isopentenyl diphosphate, but not acetyl-CoA and mevalonate [19,20]. So, an isoprene unit is derived from isopentenyl diphosphate, and can be formed via two alternative pathways, the mevalonate pathway (in eukaryotes) and the deoxyxylulose pathway in prokaryotes and plant plastids [16,19]. 

The terpenoids are secondary metabolites that are found in essential oils, resins, tissues of higher plants and micro-organisms, whilst recently some have also been located in liverworts [5,6]. The terpenoids are formed from linear arrangements of isoprene units, Fig. (1), which are derived from acetate metabolism through mevalonic acid (MVA). This pathway was found to be common to the whole range of natural terpenoid derivatives... 

METHY LISOBUTYL CARBINOI. (MIHC). Sec Ketones. METHYL1SOBUTYL KETONE (M1BKI. See Ketones. METHYLPR1D1NE. See Pyridine and Derivatives MEVALONIC ACID. See Steroids. 

In addition to acetyl-CoA, shikimic acid, mevalonic acid, and deoxyxylulose phosphate, other building blocks based on amino acids are frequently employed in natural product synthesis. Peptides, proteins, alkaloids, and many antibiotics are derived from amino acids, and the origins of the most important amino acid components of these are briefly indicated in Figure 2.1. Intermediates from the glycolytic pathway and the Krebs cycle are used in constructing many of them, but the aromatic amino acids phenylalanine, tyrosine,... 

The biochemical isoprene units may be derived by two pathways, by way of intermediates mevalonic acid (MVA) (Figure 5.4) or 1-deoxy-D-xylulose 5-phosphate (deoxyxylulose phosphate DXP) (Figure 5.6). Mevalonic acid, itself a product of acetate metabolism, had been established as a precursor of the animal sterol cholesterol, and... 

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