Precursors isoprenoid

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... 

Subsequent cyclizations, dehydrogenations, oxidations, etc., lead to the individual naturally occurring carotenoids, but little is known about the biochemistry of the many interesting final structural modifications that give rise to the hundreds of diverse natural carotenoids. The carotenoids are isoprenoid compounds and are biosynthesised by a branch of the great isoprenoid pathway from the basic C5-terpenoid precursor, isopentenyl diphosphate (IPP). The entire biosynthesis takes place in the chloroplasts (in green tissues) or chromoplasts (in yellow to red tissues). 

Recently, a potential cytosolic component of the MEP precursor pathway, xylulose kinase, has been cloned and tested for function in an Escherichia coli complementation system. " The kinase activates exogenous xylulose in the cytoplasm. DXP is the precursor for DXS, which resides in the plastid, suggesting the activated substrate must be transported into the plastid. Another xylulose kinase homologue in Arabidopsis that contains a plastid targeting sequence was not active in the E. coli system, suggesting that it may have some other function in the plastid. Perhaps plant and bacterial tissue cultures may be fed xylulose to condition accumulation of isoprenoid metabolites. 

Rodriguez-Concepcion, M. and Boronat, A., Elncidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in hacteria and plastids a metabolic milestone achieved throngh genomics. Plant Physiol. 130, 1079, 2002. Rodriguez-Concepcion, M., Early steps in isoprenoid biosynthesis multilevel regulation of the supply of common precursors in plant cells, Phytochem. Rev. 5, 1, 2006. Eisenreich, W., Rohdich, F., and Bacher, A., Deoxyxylulose phosphate pathway to terpenoids, Trends Plant Sci. 6, 78, 2001. 

Sprenger, G.A. et al.. Identification of a thiamin-dependent synthase in Escherichia coli required for the formation of the 1-deoxy-D-xylulose 5-phosphate precursor to isoprenoids, thiamin, and pyridoxol, Proc. Natl. Acad Sci. USA 94, 12857, 1997. Lange, B.M. et al., A family of transketolases that directs isoprenoid biosynthesis via a mevalonate-independent pathway, Proc. Natl. Acad Sci. USA 95, 2100, 1998. Lois, L.M. et al., Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1- deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis, Proc. Natl. Acad. Sci. USA 95, 2105, 1998. 

Hemmerlin, A. et al., A cytosolic Arabidopsis thaliana D-xylulose kinase catalyzes the phosphorylation of 1-deoxy-D-xylulose into a precursor of the plastidial isoprenoid pathway, Plant Physiol. 106, 86652, 2006. 

Boteha-Pavia, P. et al.. Regulation of carotenoid biosynthesis in plants evidence for a key role of hydroxymethylbutenyl diphosphate reductase in controhing the supply of plastidial isoprenoid precursors. Plant J. 40, 188, 2004. 

Matthews, P.D. and Wurtzel, E.T., Metabolic engineering of carotenoid accumulation in Escherichia coli by modulation of the isoprenoid precursor pool with expression of deoxyxylulose phosphate synthase, Appl. Microbiol. Biotechnol. 53, 396, 2000. 

Metabolic Engineering for Enhancing Precursor Supply for Isoprenoid Production... 

Lycopene is a carotenoid with anticancer properties. To improve the production of lycopene by increasing the IPP flux in an engineered E. coli, the dxs gene was overexpressed and enhanced lycopene production was obtained [45]. In another example, the native promoters of DXP pathway genes in the E. coli chromosome were replaced with the strong bacteriophage T5 promoter (PTs), and the increase in isoprenoid precursors resulted in improved /3-carotene production (with a titer of 6 mg/g dry cell weight) [44]. 

Evidence for de novo synthesis of pheromone components was obtained by showing that labeled acetate and mevalonate were incorporated into ipsdienol by male Ips pini [103,104]. Similarly, labeled acetate and other labeled intermediates were shown to be incorporated into frontalin in a number of Dendroctonus species [105]. Possible precursors to frontalin include 6-methyl-6-hep-ten-2-one, which was incorporated into frontalin by D. ruffipennis [106]. The precursor 6-methyl-6-hepten-2-one also was shown to be converted to bre-vicomin in the bark beetle, Dendroctonus ponderosae [107]. In addition, the expression patterns of HMG-CoA reductase and HMG-CoA synthase are tightly correlated with frontalin production in Dendroctonus jeffreyi [108, 109]. A geranyl diphosphate synthase cDNA from I. pini was also isolated, functionally expressed, and modeled [110]. These data indicate that the de novo isoprenoid biosynthetic pathway is present in bark beetles. A variety of other monoterpene alcohols such as myrcenol, pityol, and sulcitol are probably synthesized through similar pathways [111]... 

DUVOLD, T., CALI, P., BRAVO, J.-M., ROHMER, M., Incorporation of 2-C-methyl-D-erythritol, a putative isoprenoid precursor in the mevalonate-independent pathway, into ubiquinone and menaquinone of Escherichia coli, Tetrahedron Lett., 1997, 38, 6181-6184. 

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... 

Cole, S.L., Grudzien, A., Manhart, I.O., Kelly, B.L., Oakley, H., Vassar, R. (2005) Statins cause intracellular accumulation of amyloid precursor protein, P-secretase-cleaved fragments, and amyloid P-peptide via an isoprenoid-dependent mechanism. J. Biol. Chem., 280, 18755-18770. 

Wu SQ, Schalk M, Qark A, Miles RB, Coates R, Chappell J (2006) Redirection of cytoso-hc or plastidic isoprenoid precursors elevates terpene production in plants. Nat Biotechnol 24 1441-1447... 

Besumbes O, Sauret-Giieto S, Phillips MA, Imperial S, Rodn guez-Concepcion M, Boronat A. (2004) Metabolic engineering of isoprenoid biosynthesis in Arabidopsis for the production of taxadiene, the first committed precursor of taxol. Biotechnol Bioeng 88 168-175. 

Fatty acids and isoprenoids (precursor citrate—see below)... 

A metabolite, molecular entity, or some other event/ process that precedes another component in a longer sequence of events or conversions. For example, the isoprenoid metabolite squalene is a precursor of cholesterol and glucose 6-phosphate is a precursor of glycogen, ribose, and pyruvate. See Series First Order Reaction Pulse-Chase Experiments... 

The isoprenoids contribute most to the list of structural similarities in the sea and on land. They range from common classes in both ecosystems, such as drimane sesquiterpenes, to rare classes in the sea, such as the trichothecenes (Chart 8.3.11). The similarity in marine and terrestrial polyether triterpenes (Chart 8.3.12) may be seen as convergence toward chemically favored structures, starting from squalene as a biosynthetic precursor. Similar conclusions may apply to polycyclic triterpenes. 

Cell suspension cultures of Gypsophila paniculata and Saponaria officinalis produce very closely related triterpenoid saponins. Pretreatment of cell suspension cultures of G. paniculata with gypsogenin 3,0-glucuxonide (a triterpenoid saponin precursor in G. paniculata) followed by administration of [ C] acetate resulted in a marked reduction in incorporation of radioactivity into saponins and their precursors, but not into sterols and steryl glycosides [26]. Measurements of OSC activities revealed that there was no effect of elicitor treatment on CS levels in either species, but in G. paniculata AS levels went down while in S. officinalis they increased. This suggests that in these two species OSCs are regulating steps in the isoprenoid pathway and control the flux to sterols and triter-penes. 

Hunter WN. The Non-Mevalonate Pathway of Isoprenoid Precursor Bios)mthesis. Journal of Biological Chemistry 2007 282 21573-21577. 

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