RESUMEN
The medicinal plant Psychotria ipecacuanha produces ipecac alkaloids, a series of monoterpenoid-isoquinoline alkaloids such as emetine and cephaeline, whose biosynthesis derives from condensation of dopamine and secologanin. Here, we identified three cDNAs, IpeOMT1-IpeOMT3, encoding ipecac alkaloid O-methyltransferases (OMTs) from P. ipecacuanha. They were coordinately transcribed with the recently identified ipecac alkaloid beta-glucosidase Ipeglu1. Their amino acid sequences were closely related to each other and rather to the flavonoid OMTs than to the OMTs involved in benzylisoquinoline alkaloid biosynthesis. Characterization of the recombinant IpeOMT enzymes with integration of the enzymatic properties of the IpeGlu1 revealed that emetine biosynthesis branches off from N-deacetylisoipecoside through its 6-O-methylation by IpeOMT1, with a minor contribution by IpeOMT2, followed by deglucosylation by IpeGlu1. The 7-hydroxy group of the isoquinoline skeleton of the aglycon is methylated by IpeOMT3 prior to the formation of protoemetine that is condensed with a second dopamine molecule, followed by sequential O-methylations by IpeOMT2 and IpeOMT1 to form cephaeline and emetine, respectively. In addition to this central pathway of ipecac alkaloid biosynthesis, formation of all methyl derivatives of ipecac alkaloids in P. ipecacuanha could be explained by the enzymatic activities of IpeOMT1-IpeOMT3, indicating that they are sufficient for all O-methylation reactions of ipecac alkaloid biosynthesis.
Asunto(s)
Cephaelis , Eméticos/metabolismo , Emetina/análogos & derivados , Emetina/biosíntesis , Isoenzimas/metabolismo , Metiltransferasas/metabolismo , Cephaelis/anatomía & histología , Cephaelis/química , Cephaelis/enzimología , Cromatografía Liquida , Eméticos/química , Emetina/química , Isoenzimas/clasificación , Isoenzimas/genética , Metilación , Metiltransferasas/clasificación , Metiltransferasas/genética , Datos de Secuencia Molecular , Estructura Molecular , Filogenia , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Espectrometría de Masas en TándemRESUMEN
Los tratamientos de las enfermedades tumorales o de las parasitarias presentanciertos aspectos químico-farmacéuticos comunes. En este trabajo se expone unestudio comparativo entre las estructuras químicas que muestran zonas o funcionescomunes de cada grupo terapéutico. La conclusión del mismo es que, cuandose dispone de un compuesto activo en una de estas áreas, merece la pena probarloen la otra
The treatments of neoplastic and parasitary diseases present some commonchemical and pharmacological profiles. In this paper, a comparative study betweenchemical structures of each therapeutic group that have similar functions is shown. The conclusion is that every new chemical with activity in any of these areas is asuitable candidate to be tested in the other one