Regiospecific hydroxylase and O-methyltransferase for the biosynthesis of anticancer alkaloids in Tabernaemontana elegans (toad tree).

Monoterpenoid indole alkaloids (MIAs) are a structurally diverse class natural products with significant medicinal properties. Bis-MIAs, such as chemotherapeutic vinblastine and anti-autophagic conodurine, are synthesized through enzymatic coupling of monomeric MIAs, often requiring specific modifications to activate reactive centers. In this study, we report the identification and characterization of a regiospecific enzyme pair, coronaridine 11-hydroxylase (TeC11H) and 11-hydroxycoronaridine O-methyltransferase (TeHCOMT), from Tabernaemontana elegans (toad tree).

Stereochemical insights into sarpagan and akuammiline alkaloid biosynthesis.

Sarpagan and akuammiline monoterpenoid indole alkaloids (MIAs) are a class of bioactive plant-derived compounds with significant pharmaceutical potential. These alkaloids are formed through oxidative cyclization of geissoschizine, catalyzed by homologous cytochrome P450 monooxygenases (CYP) known as sarpagan bridge enzymes (SBEs) and rhazimal synthases (RHSs). However, a long-standing discrepancy exists between the expected C16 stereochemistry of enzymatic products and the stereochemistry of naturally occurring derivatives.

Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversification.

The medicinal plant Vinca minor produces vincamine, a compound used for neurodegenerative diseases, along with a diverse array of monoterpenoid indole alkaloids (MIAs) primarily within the aspidosperma and akuammiline subclasses. While recent studies have elucidated the core biosynthetic pathways for these subclasses, the transformations of key intermediates into the vast diversity of naturally occurring alkaloids remain poorly understood. In this study, we identify and characterize two promiscuous cytochrome P450 monooxygenases (CYPs) in V.