MIADIM
Deciphering the dimerization of plant alkaloids to build sustainable and secured sources of bioactive compounds.
Our mission
The shortage of essential plant-derived medicines, such as the anticancer drug vinblastine, has urged governments to rethink drug supply chains and relocate their production. A key bottleneck lies in the scarce natural accumulation of these compounds and the incomplete knowledge of their biosynthesis — particularly the enzymatic dimerization of monoterpene indole alkaloids (MIAs), a critical and still uncharacterized step in the formation of vinblastine or therapeutic compounds.
The 4-year ANR-funded MIADIM project (2026-2030) aims to unravel these mechanisms by deciphering how MIA precursors are oxidatively coupled through a sequence involving oxidation, electrophilic aromatic substitution, and tailoring reactions catalyzed by reductases and cytochrome P450s. By combining omics approaches in Madagascar periwinkle and others related MIA-producing plant species with heterologous reconstitution in yeast cell factories, MIADIM will provide both fundamental insights into MIA metabolism and a sustainable biotechnological route to these high-value compounds.
Beyond MIAs, the multi-omics pipeline developed in MIADIM is designed to be broadly applicable to the elucidation of other cryptic biosynthetic pathways, whether in plants, marine organisms, or insects, making it a versatile tool for the broader natural product community.
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