Stress-related polyketide metabolism of Dioncophyllaceae and Ancistrocladaceae.
The discovery of a novel biosynthetic pathway to isoquinoline alkaloids is described. The naphthylisoquinoline alkaloid dioncophylline A, one of the most prominent representatives of a new class of structurally and pharmacologically intriguing secondary metabolites, is shown to originate from acetate units, both molecular halves, the isoquinoline part and the naphthalene portion, being formed from identical polyketide precursors. All other tetrahydroisoquinoline alkaloids previously investigated, ultimately originate from aromatic amino acids. The novel pathway to isoquinoline alkaloids (hence acetogenic) was proved by feeding experiments with (13)C-labelled precursors administered to callus cultures of Triphyophyllum peltatum (Dioncophyllaceae), followed by NMR investigations using the potent cryoprobe methodology. The new pathway is largely stress-sensitive: upon exposure to chemical, biotic or physical stress, T. peltatum stops producing the isoquinoline part, so that the naphthalene moiety accumulates in the chemical form of naphthoquinones like plumbagin and droserone and the chiral tetralone isoshinanolone.
Bringmann
G
G
Institut für Organische Chemie der Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
Feineis
D
D
D000222:Adaptation, Physiological; D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism*; D046508:Culture Techniques; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D019684:Magnoliopsida / Q000145:classification / Q000378:metabolism*; D008958:Models, Molecular; D009020:Morphine / Q000737:chemistry / Q000378:metabolism; D013057:Spectrum Analysis
D000470:Alkaloids; D007546:Isoquinolines; C104320:dioncophylline A; D009020:Morphine