BIOSYNTHESIS OF THE ANTITUMOR ALKALOIDS OF CATHARANTHUS

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Biosynthetic mapping of indole alkaloid biosynthesis in Catharanthus roseus will be studied using cell-free incubations from modified tissue cultures and plant homogenates. The rearrangements and transformations from tryptophan and secologanin up to the complex dimeric oncolytic alkaloids vinblastine and vincristine will be examined. The mechanisms operating in vivo will be applied to the economical synthesis of a wide range of dimeric alkaloids, hitherto only available in small amounts for biological activity evaluation, using the combined strategies of partial synthesis and enzymatic transformation. Genetic manipulation of C. roseus cells will allow novel alkaloids to be isolated as well as the opportunity to increase the yield of VLB and VCR in transformed plants. High-field NMR studies of plant metabolism will be developed.