MIACYC
Unveiling the machinery driving atypical cyclisation of monoterpenoid indole alkaloids for metabolic engineering
Our mission
Plants are an inexhaustible source of pharmaceutical compounds, essential component of our pharmacopeia. Unfortunately, these natural products (NP) accumulate in minute amounts in plants while their complex structures render total chemical syntheses highly impractical, leading to the overexploitation of natural resources.
Developing new and complementary approaches to produce highly valuable NPs is thus mandatory to secure supply at midterms while preserving natural resources. This can be notably envisaged through the conversion of abundant and simpler NP precursors that can be extracted from plants commonly grown in Europe.
It’s particularly true for the monoterpenoid indole alkaloids (MIAs), a class of NP used mostly in chemotherapies which are currently produced by semisynthesis resulting in limited supplies at exhorbitant market prices. MIACYC will focus on the elucidation of an atypical C-N indole cyclization of MIAs found in the biosynthesis of three emblematic MIAs : pleiocarpamine, vincamine and strychnine. These natural products endow with pharmacological properties and occur in three plant models (see below).
While the enzymatic reactions catalyzing the C-Nindole cyclization are still poorly documented, MIACYC aims identifying the corresponding biosynthetic reactions allowing the development of a new pipeline of pathway elucidation and opening doors for a sustainable production of these compounds and their potential derivatives through yeast metabolic engineering.
Breaking news! Our new motion design about MIACYC project!
Exploiting yeasts to fight anticancer drug shortage
Read the articles from our project!
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Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast 7 novembre 2023 - 26 août 2025 Published in Nature Chemical Biology, this collaborative work demonstrates a scalable de novo manufacturing platform for bioactive monoterpenoid indole alkaloids (MIAs, plant metabolites that possess various medicinal properties) in yeast and provides a foundation for further pathway refactoring toward microbial biosynthesis of both native and new-to-nature MIAs. -
Artificial intelligence for natural product drug discovery 27 septembre 2023 - 31 mars 2026 In this review article published in Nature Reviews drug discovery, Dr Mehdi Beniddir from the ANR project, MIACYC and collaborators describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature. -
Medicinal plants enter the single-cell multi-omics era 5 août 2023 - 26 août 2025 Our new spotlight published in Trends in Plant Science, on a report by Li et al on single-cell multi-omics approach used to elucidate the architecture and regulation of anticancer alkaloid biosynthesis in medicinal plants. -
Emerging mechanistic insights into the regulation of specialized metabolism in plants 23 décembre 2022 - 23 décembre 2025 Published in Nature Plants, this review focuses on translational, transcriptional, epigenetic and chromatin-based regulation and evolution of specialized metabolism genes, a new and forefront research filed. We extrapolate to medicinal plants that synthetize rare molecules and also discuss how this new knowledge could help in improving strategies to produce useful plant-derived pharmaceuticals. -
Boosting lignan-precursor synthesis in yeast cell factories through co-factor supply optimization 2 décembre 2022 - 2 décembre 2025 Through this commentary article, we highlight the outstanding work of the Zhou’s group which recently describes a distinct approach relying on the efficient recycling of enzyme co-factors in yeast to fulfill the synthesis of caffeic acid (CaA) and ferulic acid (FA), two precursors of podophyllotoxin. We discuss how the cofactor recycling approach will undoubtedly pave the way for future high titer production of valuable natural products in yeast. -
Genome Assembly of the Medicinal Plant Voacanga thouarsii 29 juillet 2022 - 29 juillet 2025 In our new article published in Genome Biology and Evolution, we provide the first annotated reference genome of a Voacanga species that, together with the previously published MIA-producing plant genomes, will help understand evolution and diversification of MIA in plants as well as identifying MIA biosynthetic genes to enrich the molecular MIA toolbox used for production of MIA in heterologous hosts. -
The Vinca minor genome highlights conserved evolutionary traits in monoterpene indole alkaloid synthesis 18 octobre 2022 - 18 octobre 2025 The Vinca minor genome finally assembled! Our new publication in G3!The Vinca minor plant synthesizes monoterpene indole alkaloids (MIAs), which are a class of specialized metabolites displaying a wide range of bioactive- and pharmacologically important properties. V. minor mainly accumulates vincamine, which is commercially used as a nootropic. Using a combination of Oxford Nanopore Technologies long read- and Illumina short-read sequencing, a 679,098 Mb V. minor genome was assembled into 296 scaffolds with an N50 scaffold length of 6 Mb, and encoding 29,624 genes. -
Computer-Assisted Design of Sustainable Syntheses of Pharmaceuticals and Agrochemicals from Industrial Wastes 26 août 2022 - 26 août 2025 Our new highlight in ChemSusChem!
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