Biosynthesis of oxindole alkaloids: Recent advances and challenges

The monoterpenoid oxindole alkaloids (MOA) are specialized plant metabolites of pharmacological importance, whose biosynthesis is linked to a unique oxidative process of monoterpenoid indole alkaloids (MIA). These transformations arise from complex biosynthetic pathways defined by species, organs, tissues, and growth stages. Initial studies of their biosynthesis using labeled precursors date back more than five decades ago. This review shows the advances in this topic within the years 2022-2023, which highlight the research by integrative omics strategies, validating previously stated hypotheses. The MOA biosynthesis pathway is beginning to be elucidated, especially in the early and intermediate stages starting from MIA. Also, progress in the characterization of enzymes that regulate the process has been made. The discovery of a key enzyme in the formation of the spirooxindole scaffold represents a starting point for an enormous amount of work that remains to be done to clarify and understand the formation mechanisms of MOA.