A review on Mitragyna alkaloids pharmacology, biosynthesis and biotechnological insights

• Integrates ethnobotany, chemistry, and pharmacology of nine Mitragyna species. • Updates biosynthetic pathways of indole and spirooxindole alkaloids. • Summarizes pharmacology of mitragynine, rhynchophylline, and isorhynchophylline. • Reviews plant biotechnology strategies to enhance alkaloid production. • Highlights synthetic biology platforms for sustainable kratom alkaloids. Mitragyna species, known for their diverse traditional uses across various Asian countries, have gained scientific interest due to their pharmacological properties and rich phytochemical composition. This paper presents an updated overview of nine Mitragyna species that are Mitragyna speciosa, M. diversifolia, M. stipulosa, M. rubrostipulata, M. inermis , M. hirsuta , M. parvifolia , M. rotundifolia and M. tubulosa focusing on their ethnobotany, pharmacological properties, and phytochemical constituents since 2022 to 2024. Moreover, we have extensively reviewed all aspects of plant biotechnological approaches of Mitragyna species till date and updated the indole alkaloids biosynthesis and synthetic biology of kratom alkaloids. Pharmacological studies of indole alkaloids especially mitragynine, rhynchophylline and isorhynchophylline showed potential effects on the central nervous system, cardiovascular system, digestive system and peripheral nervous system. Phytochemical analysis has revealed several secondary metabolites, particularly alkaloids, along with other compounds contributing to their medicinal properties. Understanding biosynthesis pathways and employing biotechnological approaches, such as media manipulation, precursor feeding, plant growth regulators, and elicitation, offer promising opportunity for understanding indole alkaloids metabolism and enhancing alkaloid production. Furthermore, metabolic engineering and synthetic biology of mitragyna alkaloids can provide a more sustainable, consistent and scalable alternative which holds significant potential in scientific research and pharmaceutical developments.