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).

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.

Parallel evolution of methyltransferases leads to vobasine biosynthesis in and .

Monoterpenoid indole alkaloids (MIA) are one of the largest and most complex alkaloid class in nature, boasting many clinically significant drugs such as anticancer vinblastine and antiarrhythmic ajmaline. Many MIAs undergo nitrogen -methylation, altering their reactivity and affinity to the biological targets through a straightforward reaction. Remarkably, all known MIA -methyltransferases (NMT) originate from the neofunctionalization of ancestral γ-tocopherol -methyltransferases (γTMTs), a phenomenon seemingly unique to the Apocynaceae family.