Structure–function studies of tetrahydroprotoberberine N-methyltransferase reveal the molecular basis of stereoselective substrate recognitionBenzylisoquinoline alkaloids (BIAs) are a structurally diverse class of plant-specialized metabolites that have been particularly well-studied in the order Ranunculales. The N-methyltransferases (NMTs) in BIA biosynthesis can be divided into three groups according to substrate specificity and amino acid sequence. Here, we report the first crystal structures of enzyme complexes from the tetrahydroprotoberberine NMT (TNMT) subclass, specifically for GfTNMT from the yellow horned poppy (Glaucium flavum).
An N-methyltransferase from Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine enables microbial phenylalkylamine productionPhenylalkylamines, such as the plant compounds ephedrine and pseudoephedrine and the animal neurotransmitters dopamine and adrenaline, compose a large class of natural and synthetic molecules with important physiological functions and pharmaceutically valuable bioactivities. The final steps of ephedrine and pseudoephedrine biosynthesis in members of the plant genus Ephedra involve N-methylation of norephedrine and norpseudoephedrine, respectively. Here, using a plant transcriptome screen, we report the isolation and characterization of an N-methyltransferase (NMT) from Ephedra sinica able to catalyze the formation of (pseudo)ephedrine and other naturally occurring phenylalkylamines, including N-methylcathinone and N-methyl(pseudo)ephedrine.
Isolation and Characterization of Reticuline N-Methyltransferase Involved in Biosynthesis of the Aporphine Alkaloid Magnoflorine in Opium PoppyBenzylisoquinoline alkaloids are a large group of plant-specialized metabolites displaying an array of biological and pharmacological properties associated with numerous structural scaffolds and diverse functional group modification. N-Methylation is one of the most common tailoring reactions, yielding tertiary and quaternary pathway intermediates and products. Two N-methyltransferases accepting (i) early 1-benzylisoquinoline intermediates possessing a secondary amine and leading to the key branch-point intermediate (S)-reticuline and (ii) downstream protoberberines containing a tertiary amine and forming quaternary intermediates destined for phthalideisoquinolines and antimicrobial benzo[c]phenanthridines were previously characterized.