Publications of Alkaloid biosynthesis Group
Our new 2023 articles!
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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. -
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. -
The evolutionary pattern of cocaine and hyoscyamine biosynthesis provides strategies to produce tropane alkaloids 30 mai 2023 - 21 février 2026 In this highlight published in ChemBioChem, we discuss how tropane alkaloid biosynthesis evolved via the recruitment of two distinct and convergent pathways in Erythroxylaceae and Solanaceae. -
Spatial localization of monoterpenoid indole alkaloids in Rauvolfia tetraphylla by high resolution mass spectrometry imaging 21 février 2023 - 21 février 2025 In this study published in Phytochemistry, we explore how matrix assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) can be used in the investigation of a proposed biosynthetic pathway by localizing reserpine and the theoretical intermediates of it -
Convergent evolution for antibiotic biosynthesis in bacteria and animals 21 février 2023 - 21 février 2025 A spotlight in Trends in genetics about the convergent evolution for antibiotic biosynthesis in bacteria and animals.
Articles published in 2022
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An updated version of the Madagascar periwinkle genome 21 décembre 2022 - 21 décembre 2025 This updated version should ease evolutionary studies leading to a better understanding of MIA biosynthetic pathway evolution. -
Single-cell RNA sequencing provides a high-resolution roadmap for understanding the multicellular compartmentation of specialized metabolism 15 décembre 2022 - 15 décembre 2025 Read our new study with Pr Chao SUN’s group, on single-cell RNA sequencing of Catharanthus roseus leaf published in Nature 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. -
The high osmolarity glycerol (HOG) pathway in fungi 10 novembre 2022 - 10 novembre 2025 A collaborative paper which describes the HOG-mediated stress adaptation, with a particular focus on osmotic and oxidative stress, and point out some lags in our understanding of its involvement in the virulence of pathogenic species including, the medically important fungi Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, compared to the model yeast Saccharomyces cerevisiae. -
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! -
A microbial supply chain for production of the anti-cancer drug vinblastine published in NATURE! 31 août 2022 - 31 août 2025 The authors engineered yeast to produce the cancer therapeutic vinblastine. A promising achievement for the synthetis of therapeutic natural products. This is the latest research of several teams including MIAMi project collaborators. Dr Vincent Courdavault , assistant professor in our lab and Emily A. Stander, former post-doctoral researcher are co-authors of this paper published in Nature. -
Identification of a second 16-hydroxytabersonine-O-methyltransferase suggests an evolutionary relationship between alkaloid and flavonoid metabolisms in Catharanthus roseus 26 août 2022 - 26 août 2025 We identified a second isoform of 16-hydroxytabersonine-O-methyltransferase enzyme that suggests an evolutionary relationship between alkaloid and flavonoid metabolisms in the Madagascar Periwinkle, a plant producing anti-cancer drugs - our new article in Protoplasma! -
A new path for terpenoid biosynthesis 29 juillet 2022 - 29 juillet 2025 Our spotlight on the work of Tao and colleagues that discovered a new pathway for triterpene biosynthesis in which bifunctional class I terpene synthases from fungi catalyze both the synthesis of HexPP and its cyclization via their prenyltransferase (PTd) and terpene cyclase (TCd) domains. -
Towards a Better Understanding of Toxin Biosynthesis in Seaweeds 21 juin 2022 - 21 juin 2025 We discuss in this Highlight article the importance of continuing to acquire new data on biosynthetic pathways in marine organisms for both diagnostic and metabolic-engineering purposes. -
More than a Catharanthus plant: A multicellular and pluri-organelle alkaloid-producing factory 24 mars 2022 - 24 mars 2025 Spotlight on our model plant, the Madagascar periwinkle : much more than a plant, an alkaloid factory! A review in Current Opinion Plant Biology. -
Social amoebae as a new chassis for drug production 21 février 2022 - 21 février 2024 Social amoebae as a new chassis for drug production : our new spotlight published in Trends in Biotechnology -
Chromosome-scale genomes throw light on plant drug biosynthesis 14 février 2022 - 30 septembre 2024 Recent chromosome-scale genomes from prominent medicinal plants have provided unprecedent insight into the architecture and evolution of some prominent metabolic pathways. A story related in our new paper published in Trends in Pharmacological Sciences! -
RNA-seq Analysis of Monoterpene Indole Alkaloid Biosynthetic Pathway Elucidation in Catharanthus roseus 23 février 2022 In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we describe bioinformatic protocols for exploiting such coexpression to shortlist candidate genes of the well-described monoterpene indole alkaloid (MIA) pathway of Catharanthus roseus. - Predicting Monoterpene Indole Alkaloid-Related Genes from Expression Data with Artificial Neural Networks 23 février 2022 - 23 février 2025 In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, using Catharanthus roseus as an example, we show that ANN trained on a minimal set of bait genes results in many true positives (correctly predicted genes) while keeping false positives low (containing possible candidate genes).
- An Optimized Electroporation Procedure for Genetic Transformation of Candida auris 23 février 2022 - 23 février 2025 In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we provide a reliable transformation protocol based on an efficient electroporation procedure and the use of a mycophenolic acid resistance marker.
- A Rapid and Efficient Vacuum-Based Agroinfiltration Protocol for Transient Gene Overexpression in Leaves of Catharanthus roseus 23 février 2022 - 23 février 2025 In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we describe a protocol that combines a vacuum-based Agroinfiltration approach and the high translational efficiency of a deconstructed virus-based binary vector (pEAQ-HT). The described methodology is robust, easy to perform, and results in high amount of transient expression in C. roseus. This protocol is expected to serve as valuable tool to enhance the in planta characterization of gene functions or even transiently knock-in novel enzymatic activities.
- RNA In Situ Hybridization of Paraffin Sections to Characterize the Multicellular Compartmentation of Plant Secondary Metabolisms 23 février 2022 - 23 février 2025 In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we provide a step-by-step protocol describing every details allowing to reach a medium throughput including riboprobe synthesis, paraffin-embedded plant tissue array preparation, prehybridization, in situ hybridization, stringent washing and immunodetection of hybridized probes, and imaging steps.
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ARResting cytokinin signaling for salt-stress tolerance 23 janvier 2022 In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we describe bioinformatic protocols for exploiting such coexpression to shortlist candidate genes of the well-described monoterpene indole alkaloid (MIA) pathway of Catharanthus roseus. -
Marine drugs: Biology, pipelines, current and future prospects for production 13 décembre 2021 - 30 juin 2024 Do you know that marine organisms represent a huge reservoir of new pharmaceuticals? If you are interested, read our new research review paper published in Biotechnology advances!
Articles published in 2021
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.
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.
The evolutionary pattern of cocaine and hyoscyamine biosynthesis provides strategies to produce tropane alkaloids
30 mai 2023 - 21 février 2026
In this highlight published in ChemBioChem, we discuss how tropane alkaloid biosynthesis evolved via the recruitment of two distinct and convergent pathways in Erythroxylaceae and Solanaceae.
Spatial localization of monoterpenoid indole alkaloids in Rauvolfia tetraphylla by high resolution mass spectrometry imaging
21 février 2023 - 21 février 2025
In this study published in Phytochemistry, we explore how matrix assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) can be used in the investigation of a proposed biosynthetic pathway by localizing reserpine and the theoretical intermediates of it
Convergent evolution for antibiotic biosynthesis in bacteria and animals
21 février 2023 - 21 février 2025
A spotlight in Trends in genetics about the convergent evolution for antibiotic biosynthesis in bacteria and animals.
An updated version of the Madagascar periwinkle genome
21 décembre 2022 - 21 décembre 2025
This updated version should ease evolutionary studies leading to a better understanding of MIA biosynthetic pathway evolution.
Single-cell RNA sequencing provides a high-resolution roadmap for understanding the multicellular compartmentation of specialized metabolism
15 décembre 2022 - 15 décembre 2025
Read our new study with Pr Chao SUN’s group, on single-cell RNA sequencing of Catharanthus roseus leaf published in Nature 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.
The high osmolarity glycerol (HOG) pathway in fungi
10 novembre 2022 - 10 novembre 2025
A collaborative paper which describes the HOG-mediated stress adaptation, with a particular focus on osmotic and oxidative stress, and point out some lags in our understanding of its involvement in the virulence of pathogenic species including, the medically important fungi Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, compared to the model yeast Saccharomyces cerevisiae.
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!
A microbial supply chain for production of the anti-cancer drug vinblastine published in NATURE!
31 août 2022 - 31 août 2025
The authors engineered yeast to produce the cancer therapeutic vinblastine. A promising achievement for the synthetis of therapeutic natural products. This is the latest research of several teams including MIAMi project collaborators. Dr Vincent Courdavault , assistant professor in our lab and Emily A. Stander, former post-doctoral researcher are co-authors of this paper published in Nature.
Identification of a second 16-hydroxytabersonine-O-methyltransferase suggests an evolutionary relationship between alkaloid and flavonoid metabolisms in Catharanthus roseus
26 août 2022 - 26 août 2025
We identified a second isoform of 16-hydroxytabersonine-O-methyltransferase enzyme that suggests an evolutionary relationship between alkaloid and flavonoid metabolisms in the Madagascar Periwinkle, a plant producing anti-cancer drugs - our new article in Protoplasma!
A new path for terpenoid biosynthesis
29 juillet 2022 - 29 juillet 2025
Our spotlight on the work of Tao and colleagues that discovered a new pathway for triterpene biosynthesis in which bifunctional class I terpene synthases from fungi catalyze both the synthesis of HexPP and its cyclization via their prenyltransferase (PTd) and terpene cyclase (TCd) domains.
Towards a Better Understanding of Toxin Biosynthesis in Seaweeds
21 juin 2022 - 21 juin 2025
We discuss in this Highlight article the importance of continuing to acquire new data on biosynthetic pathways in marine organisms for both diagnostic and metabolic-engineering purposes.
More than a Catharanthus plant: A multicellular and pluri-organelle alkaloid-producing factory
24 mars 2022 - 24 mars 2025
Spotlight on our model plant, the Madagascar periwinkle : much more than a plant, an alkaloid factory! A review in Current Opinion Plant Biology.
Social amoebae as a new chassis for drug production
21 février 2022 - 21 février 2024
Social amoebae as a new chassis for drug production : our new spotlight published in Trends in Biotechnology
Chromosome-scale genomes throw light on plant drug biosynthesis
14 février 2022 - 30 septembre 2024
Recent chromosome-scale genomes from prominent medicinal plants have provided unprecedent insight into the architecture and evolution of some prominent metabolic pathways. A story related in our new paper published in Trends in Pharmacological Sciences!
RNA-seq Analysis of Monoterpene Indole Alkaloid Biosynthetic Pathway Elucidation in Catharanthus roseus
23 février 2022
In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we describe bioinformatic protocols for exploiting such coexpression to shortlist candidate genes of the well-described monoterpene indole alkaloid (MIA) pathway of Catharanthus roseus.
Predicting Monoterpene Indole Alkaloid-Related Genes from Expression Data with Artificial Neural Networks
23 février 2022 - 23 février 2025
In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, using Catharanthus roseus as an example, we show that ANN trained on a minimal set of bait genes results in many true positives (correctly predicted genes) while keeping false positives low (containing possible candidate genes).
An Optimized Electroporation Procedure for Genetic Transformation of Candida auris
23 février 2022 - 23 février 2025
In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we provide a reliable transformation protocol based on an efficient electroporation procedure and the use of a mycophenolic acid resistance marker.
A Rapid and Efficient Vacuum-Based Agroinfiltration Protocol for Transient Gene Overexpression in Leaves of Catharanthus roseus
23 février 2022 - 23 février 2025
In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we describe a protocol that combines a vacuum-based Agroinfiltration approach and the high translational efficiency of a deconstructed virus-based binary vector (pEAQ-HT). The described methodology is robust, easy to perform, and results in high amount of transient expression in C. roseus. This protocol is expected to serve as valuable tool to enhance the in planta characterization of gene functions or even transiently knock-in novel enzymatic activities.
RNA In Situ Hybridization of Paraffin Sections to Characterize the Multicellular Compartmentation of Plant Secondary Metabolisms
23 février 2022 - 23 février 2025
In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we provide a step-by-step protocol describing every details allowing to reach a medium throughput including riboprobe synthesis, paraffin-embedded plant tissue array preparation, prehybridization, in situ hybridization, stringent washing and immunodetection of hybridized probes, and imaging steps.
ARResting cytokinin signaling for salt-stress tolerance
23 janvier 2022
In this Chapter of the "Catharanthus roseus, Methods and Protocols" book, we describe bioinformatic protocols for exploiting such coexpression to shortlist candidate genes of the well-described monoterpene indole alkaloid (MIA) pathway of Catharanthus roseus.
Marine drugs: Biology, pipelines, current and future prospects for production
13 décembre 2021 - 30 juin 2024
Do you know that marine organisms represent a huge reservoir of new pharmaceuticals? If you are interested, read our new research review paper published in Biotechnology advances!
- Kulagina N, Besseau S, Godon C, Goldman GH, Papon N, Courdavault V. .Yeasts as Biopharmaceutical Production Platform. Front. Fungal Biol. 2021 : https://doi.org/10.3389/ffunb.2021.733492
- Koudounas K, Guirimand G, Rojas Hoyos LF, et al. Tonoplast and Peroxisome Targeting of γ-tocopherol N-methyltransferase Homologs Involved in the Synthesis of Monoterpene Indole Alkaloids [published online ahead of print, 2021 Nov 10]. Plant Cell Physiol. 2021;pcab160. doi:10.1093/pcp/pcab160
- Kulagina N, Perrin J, Besseau S, Courdavault V. Efficient Terpene Production by Marine Thraustochytrids: Shedding Light on the Thermodynamic Driving Force. mBio. 2021;12(5):e0197621. doi:10.1128/mBio.01976-21
- Yamamoto K, Grzech D, Koudounas K, et al. Improved virus-induced gene silencing allows discovery of a serpentine synthase gene in Catharanthus roseus. Plant Physiol. 2021;187(2):846-857. doi:10.1093/plphys/kiab285
- Méteignier LV, Papon N, Courdavault V. Plant to Insect Horizontal Gene Transfer: Empowering Whiteflies. Trends Genet. 2021;37(8):688-690. doi:10.1016/j.tig.2021.04.007
- Kulagina N, Guirimand G, Melin C, et al. Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories [published online ahead of print, 2021 Jul 24]. Microb Biotechnol. 2021;10.1111/1751-7915.13898. doi:10.1111/1751-7915.13898
- Stander EA, Dugé de Bernonville T, Papon N, Courdavault V. Computational biotechnology guides elucidation of the biosynthesis of the plant anticancer drug camptothecin. Comput Struct Biotechnol J. 2021;19:3659-3663. Published 2021 Jun 22. doi:10.1016/j.csbj.2021.06.028
- Lemos Cruz P, Kulagina N, Guirimand G, et al. Optimization of Tabersonine Methoxylation to Increase Vindoline Precursor Synthesis in Yeast Cell Factories. Molecules. 2021;26(12):3596. Published 2021 Jun 11. doi:10.3390/molecules26123596
- Courdavault V, O'Connor SE, Jensen MK, Papon N. Metabolic engineering for plant natural products biosynthesis: new procedures, concrete achievements and remaining limits [published online ahead of print, 2021 May 10]. Nat Prod Rep. 2021;10.1039/d0np00092b. doi:10.1039/d0np00092b
- Kulagina N, Besseau S, Papon N, Courdavault V. Peroxisomes: A New Hub for Metabolic Engineering in Yeast. Front Bioeng Biotechnol. 2021;9:659431. Published 2021 Apr 7. doi:10.3389/fbioe.2021.659431
- Carqueijeiro I, Koudounas K, Dugé de Bernonville T, et al. Alternative splicing creates a pseudo-strictosidine β-d-glucosidase modulating alkaloid synthesis in Catharanthus roseus. Plant Physiol. 2021;185(3):836-856. doi:10.1093/plphys/kiaa075
- Perrin J, Kulagina N, Unlubayir M, et al. Exploiting Spermidine N-Hydroxycinnamoyltransferase Diversity and Substrate Promiscuity to Produce Various Trihydroxycinnamoyl Spermidines and Analogues in Engineered Yeast. ACS Synth Biol. 2021;10(2):286-296. doi:10.1021/acssynbio.0c00391
- Stander EA, Papon N, Courdavault V. Puzzling Out the Colchicine Biosynthetic Pathway. ChemMedChem. 2021;16(4):621-623. doi:10.1002/cmdc.202000633
- Kulagina N, Papon N, Courdavault V. Microbial Cell Factories for Tetrahydroisoquinoline Alkaloid Production. Chembiochem. 2021;22(4):639-641. doi:10.1002/cbic.202000579
- Guirimand G, Kulagina N, Papon N, Hasunuma T, Courdavault V. Innovative Tools and Strategies for Optimizing Yeast Cell Factories. Trends Biotechnol. 2021;39(5):488-504. doi:10.1016/j.tibtech.2020.08.010
- Courdavault V, Cassereau J, Papon N. Engineered Microbes for Producing Anticholinergics. Chembiochem. 2021;22(8):1368-1370. doi:10.1002/cbic.202000757
Collaborative papers in 2021
- Djeghdir I, Chefdor F, Bertheau L, et al. Evaluation of type-B RR dimerization in poplar: A mechanism to preserve signaling specificity?. Plant Sci. 2021;313:111068. doi:10.1016/j.plantsci.2021.111068
- Roumani M, Besseau S, Gagneul D, Robin C, Larbat R. Phenolamides in plants: an update on their function, regulation, and origin of their biosynthetic enzymes. J Exp Bot. 2021;72(7):2334-2355. doi:10.1093/jxb/eraa582
- Cassereau J, Courdavault V, Nägerl UV. Turning up the Green Light. Trends Cell Biol. 2021;31(3):143-145. doi:10.1016/j.tcb.2020.12.007
