A study published in Nature Communications describes the de novo biosynthesis of the antiarrhythmic alkaloid ajmaline in Baker's yeast. Ajmaline, a monoterpenoid indole alkaloid (MIA) derived from the Ayurvedic plant Rauvolfia serpentina, is used as a diagnostic agent for Brugada syndrome. The research team identified and characterized two critical enzymes, vomilenine 1,2(R)-reductase (VR) and 1,2-dihydrovomilenine 19,20(S)-reductase (DHVR), which are essential for ajmaline biosynthesis. They also identified two root-expressing esterases, AAE1 and AAE2, which complete the biosynthesis of ajmaline. The study shows that ajmaline biosynthesis proceeds with vomilenine 1,2(R)-reduction followed by its 19,20(S)-reduction. This process is further modulated by two root-expressing esterases that deacetylate 17-O-acetylnorajmaline. The researchers engineered the de novo biosynthesis of ajmaline in Baker's yeast, demonstrating the complete biosynthetic pathway. The study also highlights the importance of understanding the biosynthesis of ajmaline and other MIAs for the development of new drugs and biotechnological applications. The findings provide a foundation for the large-scale production of ajmaline using synthetic biology approaches.A study published in Nature Communications describes the de novo biosynthesis of the antiarrhythmic alkaloid ajmaline in Baker's yeast. Ajmaline, a monoterpenoid indole alkaloid (MIA) derived from the Ayurvedic plant Rauvolfia serpentina, is used as a diagnostic agent for Brugada syndrome. The research team identified and characterized two critical enzymes, vomilenine 1,2(R)-reductase (VR) and 1,2-dihydrovomilenine 19,20(S)-reductase (DHVR), which are essential for ajmaline biosynthesis. They also identified two root-expressing esterases, AAE1 and AAE2, which complete the biosynthesis of ajmaline. The study shows that ajmaline biosynthesis proceeds with vomilenine 1,2(R)-reduction followed by its 19,20(S)-reduction. This process is further modulated by two root-expressing esterases that deacetylate 17-O-acetylnorajmaline. The researchers engineered the de novo biosynthesis of ajmaline in Baker's yeast, demonstrating the complete biosynthetic pathway. The study also highlights the importance of understanding the biosynthesis of ajmaline and other MIAs for the development of new drugs and biotechnological applications. The findings provide a foundation for the large-scale production of ajmaline using synthetic biology approaches.