Indole alkaloids precursor feeding

There are recognized at present three naturally occurring members of this group, cinchonamine, quinamine, and conquinamine, all minor alkaloids of certain Cinchona and Memijia species. The elucidation of their structures led to the suggestion that the quinoline moiety of the major bases, e.g., cinchonine and quinine, of these plants was probably derived from tryptophan via an indolic precursor. It has since been demonstrated from the results of feeding experiments with isotopically labeled tryptophan that this amino acid really can serve as a precursor of various indole alkaloids (1) as well as of quinine (2). The details of these processes are not yet known but probably involve an intermediate(s) related to cinchonamine (2, 3, 6). 

An interesting new technique has been applied to the study of indole alkaloid biosynthesis the alkaloids in Vinca rosea seedlings were examined after the administration of DL-[2 - C]tryptophan (ca. 30% incorporation) and the appearance and disappearance of radioactivity noted as a function of time. The technique is thus similar to the widely used method of 2 feeding. The results were in accord with those obtained earlier by precursor feeding. In particular,... 

Production can be increased by addition of precursors to the culture media, in which cases the precursors are not metabolized in the medium and, after uptake, appear in the right compartment of the plant cell. For C. roseus cultures, for example, it was found that increased indole alkaloid production was obtained after feeding with L-tryptophan, tryptamine, secologanin, loganin, loganic acid, or shikimic acid (20). Cell cultures have also been used for biotransformations, for example, the conversion of (-)-codeinone to (-)-codeine in Papaver somniferum cultures (100). For the tropane alkaloids a large number of precursor feeding and biotransformation studies with cultures of various solanaceous plants have been performed (see below). 

This has been justified when radioactive tryptophan or tryptamine (decarboxytryptophan) were incorporated into several indole alkaloids ( 54-57).It has also been predicted that the non-tryptophan portions of these alkaloids are formed from two mevalonate units to afford a cyclopentane monoterpenoid precursor (58,59). This was proved upon feeding dl-[2- C]-mevalonic acid lactone, and sodium ( )-[2- C] mevalonate into vinca rosea plants and resulted in the isolation of radioactive vindoline, catharan-thine and ajmalicine ( 60-64). 

Kargi F, Ports P (1991) Effect of various stress factors on indole alkaloid formation by Catharanthus roseus (periwinkle) cells. Enzyme Microb Technol 13 760-763 Moreno PRH, Van der Heijden R, Verpoorte R (1993) Effect of terpenoid precursor feeding and elicitation on formation of indole alkaloids in cell suspension cultures of Catharanthus roseus. Plant Cell Rep 12 702-705... 

In the course of their studies on the biosynthesis of ergot alkaloids. Robbers and Floss isolated clavidpitic acid, a new indolic amino acid [89]. Based on the X-ray crystal data of the major isomer and the assumption that the stereocenter at C-5 retains its stereochemistry from L-tryptophan, the structure shown in Scheme 59 was assigned [90]. By performing feeding experiments on Claviceps sp. SD 58 with clavicipitic acid (biosynthetically labeled), the laboratories of Floss [90] and Anderson [91] independently determined that clavicipitic acid is not a precursor to elymoclavine. Instead, Floss argues that it arises from ... a derailment of the metabolism leading to the tetracyclic ergolines between the first and second pathway-specific steps, the isoprenylation of tryptophan and the N-methylation of 4-(y,y-dimethylallyl)-tryptophan (DMAT). Anderson and co-workers isolated an enzyme, DMAT oxidase, from Claviceps sp. which catalyzes the formation of clavicipitic acid from DMAT [92]. The enzyme, which requires... 

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