Limonene biosynthesis

Problem 11.14 j Review the mechanism of geraniol biosynthesis shown in Figure 11.15, and then propose a mechanism for the biosynthesis of limonene from linalyl diphosphate. 

Attempts to investigate boll weevil (Anthonomus grandis) pheromone biosynthesis have identified isomerization, dehydration, and oxidation of the pheromone alcohols, and anticipated allylic oxidation of myrcene and limonene, but no evidence for the cyclization of acyclic precursors. The aggregation pheromones of bark beetles have been reviewed. Ips calligraphus responds to ipsdienol only in the presence of the c/5-verbenol (32) large additional concentrations of the enantiomer (l/ ,4i ,5/ )-(32) reduce beetle response. 5-(-)-Ipsenol, the pheromone of Ips grandicollis, increases the response of /. avulsus to its own pheromone ipsdienol. ... 

Mechanistic studies revealed that the effects of limonene on cell proliferation and cell cycle progression were preceded by a decrease in cyclin D1 messenger RNA levels [284] and inhibition of posttranslational isoprenylation, rather than through the suppression of cholesterol biosynthesis [271 279, 285-293]. Limonene and perillyl alcohol and their active serum metabolites inhibit protein isoprenylation [287, 289-291, 294]. 

Deuterium and tritium isotope effect study of the methyl-methylene elimination in the enzyme catalyzed biosynthesis of (R)- and (S)- limonenes (506)... 

Strategy Problem 6 A labelled compound for biosynthetic studies. Mevalonic acid (TM418) is an intermediate in the biosynthesis of terpenes and steroids (Tedder, volume 4, p.217 ff). To study exactly what happens to each carbon atom during its transformation into, say, limonene (418A), we need separate... 

Turner, G., Gershenzon, J., Nielson, E.E., Eroehlich, J.E. and Croteau, R. (1999) Limonene s)mthase, the enzyme responsible for monoterpene biosynthesis in peppermint, is localized to leucoplasts of oil gland secretory cells. Plant Physiol., 120, 879-86. 

Figure 3 Pathway of (-)-menthol biosynthesis in Mentha. LS, (-)-limonene synthase L30H, (-)-limonene-3-hydroxylase iPD, (-)-frans-isopiperitenol dehydrogenase iPR, (-)-isopiperitenone reductase iPI, ( + )-c/s-isopulegone isomerase PR, ( + )-pulegone reductase MR, (-)-menthone reductase.

Inhibition of cholesterol biosynthesis occurred in the small intestine of rats after administration of D-limonene for 7 days, but no significant effect on the secretion of radiolabeled cholesterol into bile and feces was observed. o-Limonene increased the perfusion pressure of the sphincter of Oddi in dogs when injected IV or directly into the common bile duct. 

Bouwmeester, H.J., Gerhenzon, J., Konigs, M.C.J.M. and Croteau, R. (1998). Biosynthesis of the monoterpenes limonene and carvone in the fruits of caraway - I. Demonstration of enzyme activities and their changes with development. Plant Physiology, 117 (3) 901-912. 

Limonene orange biosynthesis and optical isomers possible [358, 351, 352]... 

Evidence for conjugate reduction as a key step in monot-erpene biosynthesis has been obtained from studies of the oxygenated monoterpenes of Mentha piperita (Fig. 19.10) (Croteau, 1984). The pathway from isopiperitenone to the menthol esters was deduced largely by time-course studies and direct feeding experiments. Other evidence supports the intermediacy of /-limonene (11) as the first cyclization product of GPP in this plant. This is followed by the adlylic oxidation of the olefin and subsequent isomerization and reduction of the double bonds of isopiperitenone to the men-thones (such as 26). Furthermore, stereospecific dehydrogenases responsible for the synthesis of /-menthol (27) and d-neomenthol (28) have been isolated (Croteau, 1984). 

The enzymes responsible for the hydroxylation of monoterpenes such as (— )-limonene (11) from peppermint Mentha piperita), spearmint Mentha spicata), and perilla Per-ilia frutescens) have been isolated and characterized (Karp et al., 1987,1990). Microsomal preparations from the epidermal oil glands of these plants catalyze the NADPH and 02-dependent allylic hydroxylation of (- )-(45)-limonene (the major olefinic constituent of each of the three species) at C-3, C-6, and C-7, respectively, to produce (- )-rra j-isopiper-itenol (34), (- )- m 5-carveol (35), and (- )-perillyl alcohol (36) (Fig. 19.9) (Karp et al., 1990). These transformations are the key steps in the biosynthesis of oxygenated monoterpenes in the respective species. The enzymes appear to be... 

Karp, F., C. A. Mihauak, J. L. Harris, and R. Croteau, Monoter-pene biosynthesis Specificity of the hydroxylations of (-)-limonene by enzyme preparations from peppermint (Mentha piperita), spearmint (Mentha spicata), and perilla (Perilla frutescens) leaves. Arch. Biochem. Biophys., 276, 219-226 (1990). 

The substrate specificity of 1,8-cineole, a-terpineol, limonene, and terpin-olene synthetases from sage has not yet been determined however, it is quite clear that the sage preparations, and similar preparations from Citrus (George-Nascimento and Cori, 1971 Chayet et al., 1977), can utilize both GPP and NPP for the biosynthesis of monocyclic monoterpenes. Only when such cell-free preparations are free of all competing enzyme activities can the true specificities of the monoterpene synthetases be accurately determined. 

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