Dwivedi, M.; Vijay, N.

Arising from Stander et al. Communications Biology https://doi.org/10.1038/s42003-023-05574-8 (2023) Rauvolfia tetraphylla belongs to the Apocynaceae family, one of the largest plant families distributed across Mexico, Tropical America and Southeast Asia. They are known for producing pharmacologically important monoterpene indole alkaloids (MIAs), such as ajmaline, reserpiline, yohimbine and heteroyohimbanes (1). Due to their pharmaceutical properties, the biosynthetic modalities of several of these secondary metabolites have been explored (2), however, the enzymatic pathways underlying yohimbine production have remained fairly understudied. Elucidating these pathways is therefore critical to enhance our understanding of yohimbane MIA metabolism and aid in their industrial production and drug discovery. This research gap was adequately addressed in a recent edition of Communication Biology, where Stander et al. [STAN23] (3) presented a high-quality assembly for R. tetraphylla using a multi-platform high-coverage dataset. Notably, the yohimbane biosynthesis pathway was uncovered for the first time. Based on their metabolomics, proteomics and transcriptomic analysis followed by in vitro biochemical assays, two major findings emerged: (1) A medium chain dehydrogenase/reductase (MDR), yohimbane synthase (YOS) was found that produces a mixture of four diastereomers of yohimbanes (2) Three MDR transcripts (MDRT), MSTRG.5530, MSTRG.5531, and MSTRG.5534 were identified, which, in conjunction with geissoschizine synthase (GS, MSTRG.5528), produce a mixture of yohimbane isomers. However, the well-foundedness of the results is limited by a methodological oversight: the study does not take into account an independent whole-genome triplication event (WGT) in R. tetraphylla other than the one shared across Eudicotyledons, thus limiting the candidates identified in yohimbane biosynthesis and undermining the complexity of the biosynthetic modalities (4,5).