Refactoring monoterpenoid indole alkaloid production in microbial cell factories

Deliverables

Periodic newsletters

Candidate gene lists
Validated growth-coupled methyl-transferase system for 1 MIA compound
>1,000 refactored and prototyped MIA pathway designs

1000 refactored and prototyped MIA pathway designs

Complete and publish deep learning algorithm on MIA pathway optimization in yeast cell factories
Periodic newsletters (M24)

Periodic newsletters

Expression atlas
Annotated reference genome of Rauvolfia tetraphylla
Periodic newsletters (M48)

Periodic newsletters

Project website: the report will provide a functional description of the project website and its main sections.
Technology Transfer (T&T) Activities, including training to SMEs and research centers

Technology Transfer TT Activities including training to SMEs and research centers

Press release about the launching of MIAMi project will be sent to the media to disseminate the project
Data processing pipeline for omics data
Publicly available DNA Parts repository
Publicly available Bio-CAD

Publicly available BioCAD

"Final version of the ""Plan for the Use and Dissemination of the Foreground"" (PUDF)"

Final version of the Plan for the Use and Dissemination of the Foreground PUDF

Life-Cycle and Techno-Economic Assessment - Final report

LifeCycle and TechnoEconomic Assessment Final report

Establish localization patterns of alkaloids in Rauvolfia sp.

Establish localization patterns of alkaloids in Rauvolfia sp

List of identified metabolites (and corresponding accurate masses) in Rauvolfia serpentina and Rauvolfia tetraphylla plants
Publicly available SOPs
Sample preparation methods for MSI studies of various parts of the Rauvolfia serpentina and Rauvolfia tetraphylla plants

Delivery of large quantities of tabersonine, alstonine and rauwolscine

Delivery of large quantities of tabersonine alstonine and rauwolscine

First version of data management plan as required by Open Research Data Pilot

Publications

Leaves of Cannabis sativa and their trichomes studied by DESI and MALDI mass spectrometry imaging for their contents of cannabinoids and flavonoids

Author(s): Marcus Daniel Brandbjerg Bohn Lorensen, Sidra Yasmine Hayat, Niels Wellner, Nanna Bjarnholt, Christian Janfelt
Published in: 2023
Publisher: NIH
DOI: 10.1002/pca.3202

Literate programming for iterative design-build-test-learn cycles in bioengineering

Author(s): Søren Petersen, Lucas Levassor, Christine M. Pedersen, Rasmus Frandsen, Tilmann Weber, Jan Madsen, Lea G. Hansen, Jie Zhang, Ahmad K. Haidar, Jay D. Keasling, Nikolaus Sonnenchein, and Michael K. Jensen
Published in: 2023
Publisher: BioRxiv
DOI: 10.1101/2023.06.18.545451

Directed Biosynthesis of New to Nature Alkaloids in a Heterologous Nicotiana benthamiana Expression Host

Author(s): Marianna Boccia, Dagny Grzech, Adriana A. Lopes, Sarah E. O’Connor and Lorenzo Caputi
Published in: Frontiers, 2022
Publisher: Frontiers in Plant Science
DOI: 10.3389/fpls.2022.919443

Boosting lignan-precursor synthesis in yeast cell factories through co-factor supply optimization

Author(s): Jennifer Perrin, Sébastien Besseau, Nicolas Papon and Vincent Courdavault1
Published in: Frontiers, 2022
Publisher: Frontiers
DOI: 10.3389/fbioe.2022.1079801

Spatial localization of monoterpenoid indole alkaloids in Rauvolfia tetraphylla by high resolution mass spectrometry imaging

Author(s): Marcus Daniel Brandbjerg Bohn Lorensen, Nanna Bjarnholt, Benoit St-Pierre, Sarah Heinicke , Vincent Courdavault, Sarah O'Connor, Christian Janfelt
Published in: Phytochemistry, 2023
Publisher: Phytochemistry
DOI: 10.1016/j.phytochem.2023.113620

Gaining access to acetyl-CoA by peroxisomal surface display

Author(s): Thomas Perrot, Sébastien Besseau, Nicolas Papon, Vincent Courdavault
Published in: 2023
Publisher: Synthetic and Systems Biotechnology
DOI: 10.1016/j.synbio.2023.02.003

Chromosome-scale genomes throw light on plant drug biosynthesis

Author(s): Emily Amor Stander, Thomas Dugé de Bernonville, Nicolas Papon, Vincent Courdavault
Published in: Trends in Pharmacological Sciences, 2022
Publisher: Trends in Pharmacological Sciences
DOI: 10.1016/j.tips.2022.01.007

HSP70-binding motifs function as protein quality control degrons

Author(s): Amanda B. Abildgaard, Vasileios Voutsinos, Søren D. Petersen, Fia B. Larsen, Caroline Kampmeyer, Kristoffer E. Johansson, Amelie Stein, Tommer Ravid, Claes Andréasson, Michael K. Jensen, Kresten Lindorff-Larsen & Rasmus Hartmann-Petersen
Published in: 2023
Publisher: Cellular and Molecular Life Sciences
DOI: 10.1007/s00018-022-04679-3

Early and Late Steps of Quinine Biosynthesis

Author(s): Francesco Trenti, Kotaro Yamamoto, Benke Hong, Christian Paetz, Yoko Nakamura, and Sarah E. O’Connor
Published in: ACS Publications, 2021
Publisher: ACS Publications
DOI: 10.1021/acs.orglett.1c00206

Referee report. For: An updated version of the Madagascar periwinkle genome [version 1; peer review: 1 approved]

Author(s): Tatsis, Evangelos
Published in: F1000Researcg, Issue 7, 2023, ISSN 2046-1402
Publisher: F1000 Research Ltd.
DOI: 10.5256/f1000research.141880.r158640

Peroxisomes: A New Hub for Metabolic Engineering in Yeast

Author(s): Natalja Kulagina, Sébastien Besseau, Nicolas Papon and Vincent Courdavault
Published in: Frontiers in Bioengineering and Biotechnology, 2021, ISSN 2296-4185
Publisher: Frontiers in Bioengineering and Biotechnology
DOI: 10.3389/fbioe.2021.659431

Genome Assembly of the Medicinal Plant <i>Voacanga thouarsii</i>

Author(s): Clément Cuello; Emily Amor Stander; Hans J Jansen; Thomas Dugé de Bernonville; Arnaud Lanoue; Nathalie Giglioli-Guivarc'h; Nicolas Papon; Ron P Dirks; Michael Krogh Jensen; Sarah Ellen O'Connor; Sébastien Besseau; Vincent Courdavault
Published in: Genome Biology and Evolution, Issue 3, 2022, ISSN 1759-6653
Publisher: Oxford University Press
DOI: 10.1093/gbe/evac158

Tracking the Origin and Evolution of Plant Metabolites

Author(s): Christophe Duplais, Nicolas Papon, Vincent Courdavault
Published in: Trends in plant science, 2020, Page(s) 1182-1184, ISSN 1878-4372
Publisher: Trends in plant science
DOI: 10.1016/j.tplants.2020.08.010

Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds

Author(s): Samuel Alan Bradley; Jie Zhang; Michael Krogh Jensen
Published in: Frontiers in Bioengineering and Biotechnology, Vol 8 (2020), Issue 2, 2020, ISSN 2296-4185
Publisher: Frontiers in Bioengineering and Biotechnology
DOI: 10.3389/fbioe.2020.594126

A FAIR-compliant parts catalogue for genome engineering and expression control in Saccharomyces cerevisiae

Author(s): Vasil D'Ambrosio, Lea G Hansen, Jie Zhang, Emil D Jensen, Dushica Arsovska, Marcos Laloux, Tadas Jakočiūnas, Pernille Hjort, Davide De Lucrezia , Serena Marletta, Jay D Keasling and Michael K Jensen
Published in: Synth Syst Biotechnol ., Issue 16;7(2), 2022, Page(s) 657-663, ISSN 2405-805X
Publisher: KeAi Publishing Communications Ltd.
DOI: 10.1016/j.synbio.2022.02.001

Improved virus-induced gene silencing allows discovery of a serpentine synthase gene in Catharanthus roseus

Author(s): Kotaro Yamamoto; Dagny Grzech; Konstantinos Koudounas; Emily Amor Stander; Lorenzo Caputi; Tetsuro Mimura; Vincent Courdavault; Sarah E. O’Connor
Published in: Plant Physiology, Issue 5, 2021, ISSN 0032-0889
Publisher: American Society of Plant Biologists
DOI: 10.1093/plphys/kiab285

Computational biotechnology guides elucidation of the biosynthesis of the plant anticancer drug camptothecin

Author(s): Emily Amor Stander, ThomasDugé de Bernonville, Nicolas Papon, Vincent Courdavault
Published in: Computational and Structural Biotechnology Journal, 2021, ISSN 2001-0370
Publisher: Computational and Structural Biotechnology Journal
DOI: 10.1016/j.csbj.2021.06.028

Metabolic engineering for plant natural products biosynthesis: new procedures, concrete achievements and remaining limits

Author(s): Nicolas Papon; Vincent Courdavault; Sarah O'Connor; Michael Krogh Jensen
Published in: Natural Product Reports, 38(12), Issue 5, 2021, Page(s) 2145-2153, ISSN 0265-0568
Publisher: Royal Society of Chemistry
DOI: 10.1039/d0np00092b

Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories

Author(s): Natalja Kulagina, Grégory Guirimand, Céline Melin, Pamela Lemos-Cruz, Ines Carqueijeiro, Johan-Owen De Craene, Audrey Oudin, Vladimir Heredia, Konstantinos Koudounas, Marianne Unlubayir, Arnaud Lanoue, Nadine Imbault, Benoit St-Pierre, Nicolas Papon, Marc Clastre, Nathalie Giglioli-Guivarc’h, Jillian Marc, Sébastien Besseau, Vincent Courdavault
Published in: Microbial Biotechnology, 2021, Page(s) 2693-2699, ISSN 1751-7915
Publisher: Microbial Biotechnology
DOI: 10.1111/1751-7915.13898

The Vinca minor genome highlights conserved evolutionary traits in monoterpene indole alkaloid synthesis.

Author(s): Emily Amor Stander; Clément Cuello; Caroline Birer-Williams; Natalja Kulagina; Hans J Jansen; Ines Carqueijeiro; Louis-Valentin Méteignier; Valentin Vergès; Audrey Oudin; Nicolas Papon; Ron P Dirks; Michael Krogh Jensen; Sarah Ellen O’Connor; Thomas Dugé de Bernonville; Sébastien Besseau; Vincent Courdavault
Published in: G3: Genes, Genomes, Genetics, Issue 5, 2023, ISSN 2160-1836
Publisher: Genetics Society of America
DOI: 10.1093/g3journal/jkac268

Supplying plant natural products by yeast cell factories

Author(s): David Romero-Suarez, Jay D.Keasling and Michael K.Jensen1
Published in: Current Opinion in Green and Sustainable Chemistry, 2022, ISSN 2452-2236
Publisher: Elsevier BV
DOI: 10.1016/j.cogsc.2021.100567

Efficient Terpene Production by Marine Thraustochytrids: Shedding Light on the Thermodynamic Driving Force

Author(s): Natalja Kulagina, Jennifer Perrin, Sébastien Besseau, Vincent Courdavault
Published in: mBio, 2021, ISSN 2150-7511
Publisher: mBio
DOI: 10.1128/mbio.01976-21

Identifying Missing Biosynthesis Enzymes of Plant Natural Products

Author(s): Thomas Dugé de Bernonville, Nicolas Papon, Marc Clastre, Sarah E. O’Connor, Vincent Courdavault
Published in: Trends in Pharmacological Sciences, 2020, ISSN 0165-6147
Publisher: Elsevier BV
DOI: 10.1016/j.tips.2019.12.006

Evolution-guided engineering of small-molecule biosensors

Author(s): Tim Snoek, Evan K Chaberski, Francesca Ambri, Stefan Kol, Sara P Bjørn, Bo Pang, Jesus F Barajas, Ditte H Welner, Michael K Jensen, Jay D Keasling
Published in: Nucleic Acids Research, Issue 48/1, 2019, Page(s) e3-e3, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gkz954

Beyond the semi-synthetic artemisinin: metabolic engineering of plant-derived anti-cancer drugs

Author(s): Ines Carqueijeiro, Chloe Langley, Dagny Grzech, Konstantinos Koudounas, Nicolas Papon, Sarah E O’Connor, Vincent Courdavault
Published in: Current Opinion in Biotechnology, Issue 65, 2020, Page(s) 17-24, ISSN 0958-1669
Publisher: Elsevier BV
DOI: 10.1016/j.copbio.2019.11.017

Towards the Microbial Production of Plant-Derived Anticancer Drugs

Author(s): Vincent Courdavault, Sarah E. O’Connor, Audrey Oudin, Sébastien Besseau, Nicolas Papon
Published in: Trends in Cancer, Issue 6/6, 2020, Page(s) 444-448, ISSN 2405-8033
Publisher: Elsevier
DOI: 10.1016/j.trecan.2020.02.004

Virus-Induced Gene Silencing: Hush Genes to Make Them Talk

Author(s): Vincent Courdavault, Sébastien Besseau, Audrey Oudin, Nicolas Papon, Sarah Ellen O’Connor
Published in: Trends in Plant Science, Issue 25/7, 2020, Page(s) 714-715, ISSN 1360-1385
Publisher: Elsevier BV
DOI: 10.1016/j.tplants.2020.02.013

Engineering G protein-coupled receptor signalling in yeast for biotechnological and medical purposes

Author(s): Bettina Lengger, Michael K Jensen
Published in: FEMS Yeast Research, Issue 20/1, 2020, ISSN 1567-1356
Publisher: Blackwell
DOI: 10.1093/femsyr/foz087

Identifying Genes Involved in alkaloid Biosynthesis in Vinca minor Through Transcriptomics and Gene Co-Expression Analysis

Author(s): Emily A. Stander; Liuda Johana Sepúlveda; Thomas Dugé de Bernonville; Inês Carqueijeiro; Konstantinos Koudounas; Pamela Lemos Cruz; Sébastien Besseau; Arnaud Lanoue; Nicolas Papon; Nathalie Giglioli-Guivarc’h; Ron Dirks; Sarah E. O'Connor; Lucía Atehortúa; Audrey Oudin; Vincent Courdavault
Published in: Biomolecules, Issue 1, 2020, ISSN 2218-273X
Publisher: MDPI
DOI: 10.3390/biom10121595

Yeasts as Biopharmaceutical Production Platforms

Author(s): Natalja Kulagina, Sébastien Besseau, Charlotte Godon, Gustavo H. Goldman, Nicolas Papon and Vincent Courdavault
Published in: Frontiers in fungal biotechnology, 2021, ISSN 2054-3085
Publisher: Frontiers in fungal biotechnology
DOI: 10.3389/ffunb.2021.733492

A microbial supply chain for production of the anti-cancer drug vinblastine

Author(s): Jie Zhang; Lea G. Hansen; Olga Gudich; Konrad Viehrig; Lærke M. M. Lassen; Lars Schrübbers; Khem B. Adhikari; Paulina Rubaszka; Elena Carrasquer-Alvarez; Ling Chen; Vasil D’Ambrosio; Beata Lehka; Ahmad K. Haidar; Saranya Nallapareddy; Konstantina Giannakou; Marcos Laloux; Dushica Arsovska; Marcus A. K. Jørgensen; Leanne Jade G. Chan; Mette Kristensen; Hanne B. Christensen; Suresh Sudarsan; Em
Published in: Zhang , J , Hansen , L G , Gudich , O , Viehrig , K , Lassen , L M M , Schrübbers , L , Adhikari , K B , Rubaszka , P , Carrasquer-Alvarez , E , Chen , L , D’Ambrosio , V , Lehka , B , Haidar , A K , Nallapareddy , S , Giannakou , K , Laloux , M , Arsovska , D , Jørgensen , M A K , Chan , L J G , Kristensen , M , Christensen , H B , Sudarsan , S , Stander , E A , Baidoo , E , Petzold , C J , W, Issue 19, 2022, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-022-05157-3

Dietary Change Enables Robust Growth-Coupling of Heterologous Methyltransferase Activity in Yeast

Author(s): Anne Sofie Lærke Hansen, Maitreya J. Dunham, Dushica Arsovska, Jie Zhang, Jay D. Keasling, Markus J. Herrgard, and Michael K. Jensen*
Published in: ACS Synthetic Biology, 2020, Page(s) 3408–3415, ISSN 2161-5063
Publisher: American Chemical Society
DOI: 10.1021/acssynbio.0c00348

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