Biosnthesis of novel alkaloids part 1 - Metabolism of N-alkyldiamines and N-alkylnortropinones by transformed root cultures of Nicotiana and Brugmansia

A range of analogues of N-methylputrescine and tropinone were fed to transf ormed root cultures of Nicotiana rustica and/or a Brugmansia candida x aure a hybrid. These cultures were made by the transformation of the relevant pl ant species with Agrobacterium rhizogenes. A number of the metabolites, not ably those showing a relatively modest alteration in the N-alkyl substituen t, were metabolized in vivo to form homologues of the normal alkaloids bios ynthesized by these roots. These products were identified by GC/MS and comp arison with some synthetic reference materials. Analogues with major altera tions in the size of the N-alkyl substituent were not metabolized at all. I n the N, rustica cultures, the analogues fed at 1 mM significantly affected the profile of normal alkaloids, with up to a 4-fold diminution in nicotin e being found in the presence of N-n-propylputrescine. The ratio between al kaloids of the pyrrolidine series and the piperideine series was also affec ted. In contrast, the presence of the analogues in the B. candida x aurea h ybrid culture at I mM did not inhibit or substantially interfere with the a ccumulation of the normal spectrum of alkaloids. The potential for using th ese cultures to make complex novel products from simple precursors is discu ssed. (C) 1999 Elsevier Science Ltd. All rights reserved.