Sesquiterpene biosynthesis

McCASKILL, D., CROTEAU, R., Monoterpene and sesquiterpene biosynthesis in glandular trichomes of peppermint Mentha x piperita) rely exclusively on plastid-derived isopentenyl diphosphate, Planta, 1995,197,49-56. 

Cane DE (1999) Sesquiterpene biosynthesis cycliza-tion mechanisms. Comprehensive Natural Products Chemistry, Vol 2. Elsevier, Amsterdam, pp 155-200. 

Corbella A, Gariboldi P, Jommi G, Sisti M (1975) Biosynthesis of the Terpenoid Dendrobine. Early Stages of the Pathway. J Chem Soc, Chem Commun 288 Arigoni D (1975) Stereochemical Aspects of Sesquiterpene Biosynthesis. Pure Appl Chem 41 219... 

CANE, D.E., Sesquiterpene biosynthesis Cyclization mechanisms, in Comprehensive Natural Products Chemistry Isoprenoids, Including Carotenoids and Steroids, Vol 2. (D.E. Cane, ed,), Pergamon Press, Oxford. 1999, pp. 155-200. 

Billow, N. Kbnig W.A. (2000). The role of germacrene D as a precursor in sesquiterpene biosynthesis investigations of acid catalyzed, photochemically and thermally induced rearraneements. Phytochemistry, Vol.55, No.2, (September 2000), pp. 141-168, ISSN 0031-9422... 

Arigoni, D. Stereochemical Aspects of Sesquiterpene Biosynthesis. Pure Appl. Chem. 41, 219(1974). 

As is the case in monoterpene and sesquiterpene biosynthesis, overall incorporation of mevalonic acid (MVA) and other terpenoid precursors is low (about 1%) (Loomis and Croteau, 1980). 

Fig. 13. Possible enzyme-bound intermediates in sesquiterpene biosynthesis.

Harada H, Shindo K, Iki K, Teraoka A, Okamoto S, Yu F, Hattan J-i, Utsumi R, Misawa N (2011) Efficient functional analysis system for cyanobacte-rial or plant cytochromes P450 involved in sesquiterpene biosynthesis. Appl Microbiol Biotechnol 90 467 76... 

Scheme 87.18 Ring closing mechanisms of sesquiterpene biosynthesis...

Famesyl diphosphate (FPP) is the starting molecule for the committed step in sesquiterpene biosynthesis, so artemisinin is synthesized from FPP via the mevalonate pathway in the cytosol (Fig. 89.15). A rational approach has enhanced artemisinin yields by the overexpression of famesyl diphosphate synthase... 

Sallaud C, Rontein D, Onillon S, Jabes F, Duffe P, Giacalone C, Thoraval S, Escoffier C, Herbette G, Leonhardt N, Causse M, Tissier A (2009) A novel pathway for sesquiterpene biosynthesis from Z, Z-famesyl pyrophosphate in the wild tomato Solanum habrochaites. Plant Cell 21 301-317... 

An impressive amount of biosynthetic work in the area of sesquiterpenoids has been carried out and the results essentially confirm the aboye biogenetic theories. Ingenious tracer experiments have been devised to extract detailed stereochemical information in many cases. However, most of this work was performed on fungal metabolites, and it is not the purpose of this article to discuss details of biosynthetic studies, which will be found elsewhere (12, 19, 77, 90, 110). One basic question, though - namely the mandatory role of c-FPP in sesquiterpene biosynthesis - calls for a brief comment. 

Arigoni D 1975 Stereochemical aspects of sesquiterpene biosynthesis. Pure Appl Chem 41 219-245... 

Futatsugi K, Yamamoto H (2005) Studies on the mechanism of sesquiterpene biosynthesis, humulene-germacrene rearrangement Angew Chem Int Ed 44 1924-1942... 

The PEG precipitate (30- 0%) obtained from the 100,000 g supernatant of the epicarp of immature fruits of calamondin was submitted to chromatography on a column of DEAE-Sephacel and developed with a linear gradient of NaCl (0.1-0.2M). As shown in fig. 1, the limonene and selinene cyclase activities were resolved. The electrophoresis of the fractions involved in mono- and sesquiterpene biosynthesis showed the purification obtained after the DEAE-Sephacel column. Incubations of small gel pieces with [ H]-GPP and [ H]-FPP led to the localization of the cyclases involved in both limonene and selinene synthesis and indicated that the two cyclases are well separated on the gel. In order to improve the purification of these cyclases, the active fractions eluted from the DEAE-Sephacel column were submitted to affinity chromatography using Sepharose APP. This procedure contributed to a 90-fold and 70-fold purification for limonene and selinene cyclases respectively. An isoelectric point of 5A 0.2 was found for limonene-cyclase whereas 3-selinene-cy-clase presented a value of 6 0.2. After gel permeation with Sephadex G 200, the same molecular weight of 67 3 kD was attributed to the two cyclases. In addition, prenyltransferases obtained from a DEAE-Sephacel column developed with a step gradient (0.1, 0.2, 0.3 M NaCl) were also isolated on the same affinity column. These prenyltransferases were 160 fold purified. Their molecular weight was about 70 kD and they exhibited an isoelectric point of 3.2. 

Gleizes M., Marpeau A., Pauly G. and Bernard-Dagan C., 198 - Sesquiterpene biosynthesis in maritime pine needles. Phytochemistry 23 1237-1239. 

This does not mean that all sesquiterpene biosynthesis is independent of the 1-DXP pathway, however. In one plant system, quite the opposite has been found to be true. Bis-abolol oxides (85 and 86), matricin (81) and chamazulene (82) from chamomile flowers have been shown to contain two isoprene units derived from the 1-DXP pathway and one derived at least partially from the mevalonate pathway (Adam et al. 1999). A proposed explanation for this labelling pattern is shown in Figure 3.30. Here, sesquiterpene biosynthesis is thought to begin, unusually, in the plastids with the formation of IPP and GPP via... 

Figure 3.30 Compartmentation of sesquiterpene biosynthesis in chamomile as proposed by Adam etal. (1 999). Blocks represent isoprenoid precursor units (IPP or DMAPP).

The full details of sesquiterpene biosynthesis in chamomile are not yet known. Isolation of the prenyltransferase(s) responsible for the final steps in the biosynthesis and identification of the site of biosynthesis are likely to shed further light on the conundrum of biosynthetic compartmentation in flowering plants. These studies may also offer a challenge to the accepted wisdom that sesquiterpene biosynthesis in other flowering plants is always simply a matter of the processing of mevalonate-derived FPP in the cytosol. 

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