Terpenoid indole alkaloids secologanin, pathway

Fig. (3). Compartmentalization of the biosynthetic pathway of terpenoid indole alkaloids in plant cells. G10H geraniol 16-hydroxylase SLS secologanin synthase TDC tryptophan decarboxylase STR strictosidine synthase SGD strictosidine P-D-glucosidade T16H tabersonine 16-hydroxylase OMT S-adenosyl - L-methionine 16-hydroxytabereonine - 16-O-methyltransferase NMT S-adenosyl - /.-methionine 16-methoxy - 2,3-dihydro-3-hydroxytabersonine - A -methyltransferase D4H desacetoxy vindoline 4-hydroxylase DAT acetylcoenzyme A 4-O-deacetylvindoline 4-O-aeetyltransferase PRX peroxidase.

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... 

Terpenoid indole alkaloid biosynthesis actually starts with the coupling of tryptamine and secologanin (Fig. 12). In the next step, a glucosidase splits off the sugar moiety and the reactive dialdehyde formed is further converted through different pathways to a cascade of products, including ajmalicine, catharanthine, tabersonine, and vindoline. 

The biosynthesis of the terpenoid indole alkaloids in C. roseus has been studied extensively, but still the pathway has not yet been completely elucidated on the level of the intermediates. Particularly, the secoiridoid pathway, and the different pathways after strictosidine leading to, for example, tabersonine and catharanthine are not yet completely known. On the level of the enzymes, certain steps have now been quite well characterized, but others remain unknown. The conversion of loganin into secologanin is one of the intriguing unresolved problems, although it is not a rate-limiting step. Even possible intermediates and the chemical mechanism behind this conversion are not clear, despite quite extensive studies. 

Elucidation of the biosynthetic pathway leading from tryptamine and secologanin, the basic precursors of terpenoid indole alkaloids, to ajmalicine, 19-epiajmalicine, and tetrahydroalstonine was reviewed by Zenk (593) and Verpoorte (594). As both ajmalicine and serpentine are produced in cell cultures, most research has involved improving yields to commercially interesting levels. We here discuss various approaches to meet this goal. 

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