title: Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids aphelandrine and orantine in Aphelandra sp.
abstract: A crucial step in the biosynthesis of the spermine alkaloid aphelandrine and its diastereoisomer orantine is an intramolecular cyclization of the intermediate (S)-dihydroxyverbacine. In order to elucidate this step of the biosynthetic pathway, microsomes from the roots of Aphelandra squarrosa Nees were incubated with unlabeled and (D8)-labeled (S)-dihydroxyverbacine. It was shown that the microsomal fraction catalyzes the intramolecular coupling of (S)-dihydroxyverbacine to aphelandrine. This was proven by microsomal transformation of (D8)-labeled (S)-dihydroxyverbacine to (D8)-labeled aphelandrine. The reaction absolutely requires NAPDH and O2. The underlying reaction mechanism is probably an oxidative phenol coupling catalyzed by an aphelandrine synthase. This enzyme is proposed to be a cytochrome P-450 oxidase. The intramolecular cyclization of (S)-dihydroxyverbacine represents an important point in the biogenesis of the aphelandrine-type alkaloids.
authors.affiliation: Organisch-chemisches Institut der Universität Zürich, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Nezbedová
authors.forename: M
authors.initials: M
authors.lastname: Hesse
authors.forename: K
authors.initials: K
authors.lastname: Drandarov
authors.forename: L
authors.initials: L
authors.lastname: Bigler
authors.forename: C
authors.initials: C
authors.lastname: Werner
mesh_terms: D027901:Acanthaceae / Q000737:chemistry / Q000378:metabolism*; D000470:Alkaloids / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism*; D007769:Lactams / Q000378:metabolism*; D008027:Light; D008861:Microsomes / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D013096:Spermine / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D006576:Heterocyclic Compounds, 4 or More Rings; D007769:Lactams; D010636:Phenols; C457221:dihydroxyverbacine; D013096:Spermine; C457220:aphelandrine; C067643:orantine; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen