Geraniol Catharanthus roseus

Geraniol 10 hydroxylase catalyzes the the cytochrome P450 dependent hydroxylation of geraniol at the C-10 position to commit this substrate to the formation of iridoid monoterpenoids (Fig. 8.2). In Catharanthus roseus, this intermediate is converted to secologanin for producing the tryptamine containing monoterpenoid indole alkaloids characteristic of this plant. 

Fig. 8.1 Sequence of reactions and pathways involved in the biosynthesis of indole alkaloids in Catharanthus roseus. The dotted lines indicate multiple and/or uncharacterized enzyme steps. Tryptophan decarboxylase (TDC), Geraniol Hydroxylase (GH), Deoxyloganin synthase (DS), Secologanin Synthase (SLS) Strictosidine synthase (STR1), Strictosidine glucosidase (SG), Tabersonine-16-hydroxylase (T16H), Tabersonine 6,7-eposidase (T6,7E), Desacetoxyvindoline-4-hydroxylase (D4H), Deacetyl-vindoline-4-O-acetyltransferase (DAT) and Minovincinine-19-O-acetyltransferase (MAT) represent some of the enzyme steps that have been characterized.

MEIJER, A.H., DE WAAL, A., VERPOORTE, R., Purification of cytochrome P450 enzyme geraniol 10 hydroxylase from cell cultures of Catharanthus roseus., J. Chromatog., 1993,35,237-249. 

Figure 2.12 A hypothetical view of compartmentation of indole alkaloid biosynthesis in Catharanthus roseus. Enzymes located with dashed arrows are hypothetical and circles indicate membrane associated enzymes (after Meijer et at, 1 993b). Cl OH, geraniol-1 0-hydroxylase NMT, 5-adenosyl-L-methionine 11 -methoxy 2,16-dihydro-16-hydroxytabersonine N-methyltransferase DAT, acetylcoenzyme A deacetylvindoline 1 7-0-acetyltransferase OHT, 2-oxyglutarate-dependent dioxygenase SSpC, strictosidine-((3)-glucosidase SSS, strictosidine synthase.

Buriat, V., Oudin, A., Courtois, M., Rideau, M. and St. Pierre, B. (2004) Co-expression of three MEP pathway genes and geraniol-lO-hydroxylase in internal phloem parenchyma of Catharanthus roseus implicates multicellular location of intermediates during the biosynthesis of monoterpene indole alkaloids and isoprenoid-derived primary metabolites. Plant., 38,131 1. 

Fretz, H. and Woggon, W.-D. (1986) Regioselectivity and deuterium isotope effects in geraniol hydroxylation by the cytochrome P450 monooxygenase from Catharanthus roseus (L.). G. Don. Helv. Chim. Acta, 69, 1959-70. 

Schiel, O., Witte, L. and Berlin, J. (1987) Geraniol-lO-hydroxylase activity and its relation to monoterpene indole alkaloid accumulation in cell suspension cultures of Catharanthus roseus. Z. Naturforsch., 42c, 1075-81. 

Fig. (4). Early steps of the biosynthesis of terpenoid indole alkaloids in Catharanthus roseus. Triple arrowheads indicate multiple steps. G10H geraniol 16-hydroxylase TDC tryptophan decarboxylase STR strictosidine synthase.

FIGURE 19.11 The biotransformation of geraniol (271) and nerol (272) by Catharanthus roseus. (Modi ed from Hamada, H. and Yasumune, H., The hydroxylation of monoterpenoids by plant cell biotransformation. Proceedings of 39th TEAC, 1995, pp. 375-371)... 

It was first shown, using C-labelled mevalonate, that ajmalicine [162], catharanthine [162] and vindoline [162-165] in Catharanthus roseus as well as other alkaloids in Catharanthus roseus [162], Rauwolfia serpentina [166] and Rhazia stricta [162] gave the appropriate specific incorporation consistent with a monoterpenoid origin for the C q (or Cg) fragment additional to the trypt-amine-derived [167, 168] moiety. This work was rapidly followed by independent demonstrations [169-172] that [2- C]geraniol and its pyrophosphate, which is to be regarded as the prototype monoterpenoid in Nature, are incor-... 

Plant suspension cells of Catharanthus roseus converted geraniol (271) to 8-hydroxygeraniol (300). The same cells converted citronellol (258) to 8- (265) and 10-hydroxycitronellol (264) (Hamada et al., 2004) (Figure 14.13). 

FIGURE 14.13 Biotransformation of geraniol (271), citronellol (258), and linalool (206) by plant suspension cells of Catharanthus roseus. (Modified from Hamada, H. et al., 2004. Proc. 48th TEAC, pp. 393-395.)... 

Peebles C, Sander GW, Hughes EH, Peacock R, Shanks JV, San KY (2011) The expression of 1-deoxy-D-xylulose synthase and geraniol-lO-hydroxylase or anthranilate synthase increases terpenoid indole alkaloid accumulation in Catharanthus roseus hairy roots. Metab Eng 13 234-240. doi 10.1016/j.ymben.2010.11.005... 

Geraniol 10-hydroxylase (CYP76B6) from Catharanthus roseus is a key regulatory enzyme in the synthesis of the terpene indole alkaloid vindoline [51]. Alkaloids such as vincristine and vinblastine (derived from vindoline) are used in modem medicine as anti-neoplastic agents (Fig. 3). 

In the present review we divide the pathway leading to the Catharanthus alkaloids into five parts (Fig. 2). The first two concern the biosynthesis of tryptophan and geraniol diphosphate they are similar to (or even part of) primary metabolism and occur in all plant species. Whether these pathways in C. roseus are differently regulated, or whether even an additional pathway exists parallel to the normal primary metabolism, is a question not yet answered. The third and the fourth part coneern the steps from tryptophan to tryptamine and from geraniol to secologanin, respectively. Both pathways occur also in other plants, including plants that do not produce terpenoid indole alkaloids. The fifth part is the condensation of secologanin and tryptamine to strictosidine and the subsequent conversion into a plethora... 

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