METASYS Articles


Millard P, Delépine B, Guionnet M, Heuillet M, Bellvert F, Létisse F. IsoCor: isotope correction for high-resolution MS labeling experiments. Bioinformatics, doi: 10.1093/bioinformatics/btz209


Cox N, Kuemmerle R, Millard P, Cahoreau ., François JM, Parrou JL, Lippens G. An integrated pH meter during reaction monitoring with dual reception 1H, 31P NMR spectroscopy. Analytical Chemistry, 2019 Mar 19;91(6):3959-3963; doi: 10.1021/acs.analchem.8b05147.



Millard P, Lippens G. Interact: Automated analysis of protein-ligand interactions by 2D NMR. bioRxiv preprint, doi: 10.1101/215194.


Stuani L, Riols F, Millard P, Sabatier M, Batut A, Saland E, Viars F, Tonini L, Zaghdoudi S, Linares L, Portais JC, Sarry JE and Bertrand-Michel J. Stable isotope labeling highlights enhanced fatty acid and lipid metabolism in human acute myeloid leukemia. International Journal of Molecular Sciences, 19, 3325; doi:10.3390/ijms19113325. IF=3.7


Patacq C, Chaudet N, Létisse F. Absolute Quantification of ppGpp and pppGpp by Double-Spike Isotope Dilution Ion Chromatography-High-Resolution Mass Spectrometry. Analytical Chemistry, 2018 Sep 18;90(18):10715-10723. IF= 6.04


Trichez D, Auriol C, Baylac A, Irague R, Dressaire C, Carnicer-Heras M, Heux S, François JM, Walther T. Engineering of Escherichia coli for Krebs cycle-dependent production of malic acid. Microbial Cell Factories, 2018 Jul 16;17(1):113.  DOI : 10.1186/s12934-018-0959-y IF=3,8


Cottret L, Frainay C, Chazaviel M, Cabanettes F, Gloaguen Y, Camenen E, Merlet B, Heux S, Portais JC, Poupin N, Vinson F, Jourdan F. MetExplore: collaborative edition and exploration of metabolic networks. Nucleic Acids Research, 2018 Jul 2;46(W1):W495-W502 - IF=11,5


Heuillet M, Bellvert F, Cahoreau E, Letisse F, Millard P, Portais JC. A methodology for the validation of isotopic analyses by mass spectrometry in stable-isotope labelling experiments. Analytical Chemistry, 2018 Feb 6;90(3):1852-1860. - IF=6,0


Lippens G, Cahoreau E, Millard P, Charlier C, Lopez J, Hanoulle X and Portais JC. In-cell NMR: from metabolites to macromolecules. Analyst, 2018 Feb 7;143[3]:620-629. doi: 10.1039/c7an01635b. IF=3,9


Quedeville V, Ouazaite H, Polizzi B, Fox RO, Villedieu P, Fede P, Létisse F, Morchain J. A two-dimensional population balance model for cell growth including multiple uptake systems. Chemical Engineering Research and Design, 2018. - IF=2,8


Sinnaeve D, Dinclaux M, Cahoreau E, Millard P, Portais JC, Létisse F, Lippens G. Improved Isotopic Profiling by Pure Shift Heteronuclear 2D J-Resolved NMR Spectroscopy. Analytical Chemistry, 2018 Mar 20;90(6):4025-4031. doi: 10.1021/acs.analchem.7b05206. IF=6,0


Book chapter:

Heux S, Brautaset T, Vorholt JA, Wendisch VF, Portais JC. Synthetic Methylotrophy: Past, Present, and Future. In: Kalyuzhnaya M, Xing XH (eds) Methane Biocatalysis: Paving the Way to Sustainability. Springer, Cham, 2018



Sylvie Létoffé, Sabina Chalabaev, José Dugay, Franziska Stressmann, Bianca Audrain, Jean-Charles Portais, Fabien Letisse and Jean-Marc Ghigo. Biofilm microenvironment induces a widespread adaptive amino-acid fermentation pathway conferring strong fitness advantage in Escherichia coli. Plos Genetics, 2017 May 19;13(5):e1006800.


Sarah Schatschneider, Jessica Schneider, Jochen Blom, Fabien Létisse, Karsten Niehaus, Frank-Jörg Vorhölter, Alexander Goesmann. Systems and synthetic biology perspective of the versatile plant-pathogenic and polysaccharide-producing bacterium Xanthomonas campestris, Microbiology, 2017 Aug;163(8):1117-1144.


Alberto Rodriguez, Juan A. Martínez, Guillermo Gosset, Jean-Charles Portais, Fabien Létisse, and Francisco Bolivar. Plasmid-encoded biosynthetic genes alleviate metabolic disadvantages while increasing glucose conversion to shikimate in an engineered Escherichia coli strain. Biotechnology & Bioengineering, 2017 Jun;114(6):1319-1330.


Brice Enjalbert, Pierre Millard, Mickael Dinclaux, Jean-Charles Portais and Fabien Létisse. Acetate fluxes in Escherichia coli are determined by the thermodynamic control of the Pta-AckA pathway. Scientific Reports, 2017, 7:42135.


Fréderic Angles, Marie-Pierre Castanié-Cornet, Nawel Slama, Mickael Dinclaux, Anne-Marie Cirinesi, Jean-Charles Portais, Fabien Létisse# and Pierre Genevaux#. Multilevel interaction of the DnaK/DnaJ(HSP70/HSP40) stress-responsive chaperone machine with the central metabolism. Scientific Reports, 2017, 7:41341.


Stéphanie Heux, Cécila Bergès, Pierre Millard, Jean-Charles Portais and Fabien Létisse. Recent advances in high-throughput 13C-fluxomics. Current Opinion in Biotechnology, 2016, 43:104-109.


Millard P, Smallbone K, Mendes P: Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli. PLoS computational biology 2017, 13(2):e1005396.


Millard P, Cahoreau E, Heuillet M, Portais JC, Lippens G: 15N-NMR-Based Approach for Amino Acids-Based 13C-Metabolic Flux Analysis of Metabolism. Analytical chemistry 2017, 89(3):2101-2106.


Morin M, Ropers D, Cinquemani E, Portais JC, Enjalbert B, Cocaign-Bousquet M. 2017. The Csr system regulates Escherichia coli fitness by controlling glycogen accumulation and energy levels. MBio. 31;8(5). pii: e01628-17.


A methodology for the validation of isotopic analyses by mass spectrometry in stable-isotope labelling experiments - Heuillet M, Bellvert F, Cahoreau E, Letisse F, Millard P, Portais JC – Analytical Chemistry - doi: 10.1021/acs.analchem.7b03886





Heux, Stéphanie; Berges, Cecilia; Millard, Pierre; Portais Jean-Charles; Letisse Fabien. Recent advances in high-throughput 13C-fluxomics. Curr Opin Biotechnol. 2017 Feb;43:104-109. doi: 10.1016/j.copbio.2016.10.010. Epub 2016 Nov 10.


Tauzin A.S., Laville E., Xiao Y., Nouaille S., Le Bourgeois P., Heux S., Portais J.C., Monsan P.,  Martens E.C., Potocki-Veronese G., Bordes F. (2016) Functional characterization of a gene locus from an uncultured gut Bacteroides conferring xylo-oligosaccharides utilization to Escherichia coli. MOLECULAR MICROBIOLOGY   Volume: 102   Issue: 4   Pages: 579-592   Published: NOV 2016


Treitz C., Enjalbert B., Portais J.C., Letisse .F, Tholey A. Differential quantitative proteome analysis of Escherichia coli grown on acetate versus glucose. PROTEOMICS   Volume: 16   Issue: 21   Pages: 2742-2746   Published: NOV 2016


Lacroix, Matthieu; Rodier, Genevieve; Kirsh, Olivier; et al.  E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Volume: 113   Issue: 39   Pages: 10998-11003   Published: SEP 27 2016


Riscal, Romain; Schrepfer, Emilie; Arena, Giuseppe; et al. Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53. MOLECULAR CELL   Volume: 62   Issue: 6   Pages: 890-902   Published: JUN 16 2016


Carnicer, Marc; Vieira, Gilles; Brautaset, Trygve; et al. Quantitative metabolomics of the thermophilic methylotroph Bacillus methanolicus. MICROBIAL CELL FACTORIES   Volume: 15     Article Number: 92   Published: JUN 1 2016


Morin, Manon; Ropers, Delphine; Letisse, Fabien; et al. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli. MOLECULAR MICROBIOLOGY   Volume: 100   Issue: 4   Pages: 686-700   Published: MAY 2016


Boutzen, Helena; Saland, Estelle; Larrue, Clement; et al. Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia. JOURNAL OF EXPERIMENTAL MEDICINE   Volume: 213   Issue: 4   Pages: 483-497   Published: APR 4 2016


Ryffel, Florian; Helfrich, Eric J. N.; Kiefer, Patrick; et al. Metabolic footprint of epiphytic bacteria on Arabidopsis thaliana leaves. ISME JOURNAL   Volume: 10   Issue: 3   Pages: 632-643   Published: MAR 2016


Daguzan, C., Moulin, M., Kulyk-Barbier, H., Davrinche, C., Peyrottes, S., & Champagne, E. (2016). Aminobisphosphonates synergize with human cytomegalovirus to activate the antiviral activity of Vγ9Vδ2 cells. The Journal of Immunology, 196(5), 2219-2229.



Heux S, Meynial-Salles I, O'Donohue MJ, Dumon C. White biotechnology: State of the art strategies for the development of biocatalysts for biorefining. Biotechnol Adv. 2015 33:1653-70. 


Smallbone K, Millard P: Multi-scale modelling of E. coli metabolism. PeerJ PrePrints, 3, e1128. DOI : 10.7287/peerj.preprints.914v1


Stanford NJ, Millard P, Swainston N: RobOKoD: microbial strain design for (over)production of target compounds. Front Cell Dev Biol, 3(17). DOI : 10.3389/fcell.2015.00017


Saulou-Bérion,C., Gonzalez, I., Enjalbert, B., Audinot, J.N., Fourquaux, I., Jamme, F., Cocaign-Bousquet, M., Mercier-Bonin, & M., Girbal, L. (2015) Escherichia coli under ionic silver stress: an integrative approach to explore transcriptional, physiological and biochemical responses. PLoS One. 10(12):e0145748.


Brissac T, Ziveri J, Ramond E, Tros F, Kock S, Dupuis M, Brillet M, Barel M, Peyriga L, Cahoreau E, Charbit A. Gluconeogenesis, an essential metabolic pathway for pathogenic Francisella. Mol Microbiol. 2015, 98:518-34.


Sokol S, Portais JC. Theoretical Basis for Dynamic Label Propagation in Stationary Metabolic Networks under Step and Periodic Inputs. PLoS One. 2015 10:e0144652.


Millard P, Portais JC, Mendes P. Impact of kinetic isotope effects in isotopic studies of metabolic systems. BMC Syst Biol. 2015 9:64. 


Lennart Leßmeier, Johannes Pfeifenschneider, Marc Carnicer Heras, Stephanie Heux, Jean-Charles Portais & Volker F. Wendisch. Production of cadaverine by engineered C. glutamicum using methanol as co-substrate. Appl Microbiol Biotechnol. 2015 99:10163-76. 


Brice Enjalbert, Muriel Cocaign-Bousquet, Jean-Charles Portais, and Fabien Letisse. Acetate exposure determines the diauxic behavior of Escherichia coli during the glucose-acetate transition. J Bacteriol. 2015 197:3173-81.


Florian Ryffel, Eric J.N. Helfrich, Patrick Kiefer, Lindsay Peyriga, Jean-Charles Portais, Jörn Piel, Julia A. Vorholt. Metabolic footprint of epiphytic bacteria on Arabidopsis thaliana leaves. ISME J. 2015 Aug 25. doi: 10.1038/ismej.2015.141.


Müller JE, Meyer F, Litsanov B, Kiefer P, Potthoff E, Heux S, Quax WJ, Wendisch VF, Brautaset T, Portais JC, Vorholt JA. Engineering Escherichia coli for methanol conversion. Metab Eng. 2015, 28:190-201.




Walther T, Letisse F, Peyriga L, Alkim C, Liu Y, Lardenois A, Martin-Yken H, Portais JC, Primig M, Francois J: Developmental stage dependent metabolic regulation during meiotic differentiation in budding yeast. BMC biology 2014, 12:60.

Vieira G, Carnicer M, Portais JC, Heux S: FindPath: a Matlab solution for in silico design of synthetic metabolic pathways. Bioinformatics 2014, 30:2986-2988.

Silva RR, Jourdan F, Salvanha DM, Letisse F, Jamin EL, Guidetti-Gonzalez S, Labate CA, Vencio RZ: ProbMetab: an R package for Bayesian probabilistic annotation of LC-MS-based metabolomics. Bioinformatics 2014, 30:1336-1337.

Millard P, Sokol S, Letisse F, Portais JC: IsoDesign: a software for optimizing the design of 13C-metabolic flux analysis experiments. Biotechnology and bioengineering 2014, 111:202-208.

Millard P, Massou S, Wittmann C, Portais JC, Letisse F: Sampling of intracellular metabolites for stationary and non-stationary (13)C metabolic flux analysis in Escherichia coli. Analytical biochemistry 2014, 465:38-49.

Millard P, Massou S, Portais JC, Letisse F: Isotopic studies of metabolic systems by mass spectrometry: using Pascal's triangle to produce biological standards with fully controlled labeling patterns. Analytical chemistry 2014, 86:10288-10295.

Millard P, Letisse F, Sokol S, Portais JC: Correction of MS data for naturally occurring isotopes in isotope labelling experiments. Methods in molecular biology 2014, 1191:197-207.

Heux S, Poinot J, Massou S, Sokol S, Portais JC: A novel platform for automated high-throughput fluxome profiling of metabolic variants. Metabolic engineering 2014, 25:8-19.

Xu YF, Letisse F, Absalan F, Lu W, Kuznetsova E, Brown G, Caudy AA, Yakunin AF, Broach JR, Rabinowitz JD: Nucleotide degradation and ribose salvage in yeast. Molecular systems biology 2013, 9:665.


Revelles O, Millard P, Nougayrede JP, Dobrindt U, Oswald E, Letisse F, Portais JC: The carbon storage regulator (Csr) system exerts a nutrient-specific control over central metabolism in Escherichia coli strain Nissle 1917. PloS one 2013, 8:e66386.

Enjalbert B, Letisse F, Portais JC: Physiological and Molecular Timing of the Glucose to Acetate Transition in Escherichia coli. Metabolites 2013, 3:820-837.

Boisseau R, Charrier B, Massou S, Portais JC, Akoka S, Giraudeau P: Fast spatially encoded 3D NMR strategies for (13)C-based metabolic flux analysis. Analytical chemistry 2013, 85:9751-9757.


Sokol S, Millard P, Portais JC: influx_s: increasing numerical stability and precision for metabolic flux analysis in isotope labelling experiments. Bioinformatics 2012, 28:687-693.

Schneider K, Peyraud R, Kiefer P, Christen P, Delmotte N, Massou S, Portais JC, Vorholt JA: The ethylmalonyl-CoA pathway is used in place of the glyoxylate cycle by Methylobacterium extorquens AM1 during growth on acetate. The Journal of biological chemistry 2012, 287:757-766.

Peyraud R, Kiefer P, Christen P, Portais JC, Vorholt JA: Co-consumption of methanol and succinate by Methylobacterium extorquens AM1. PloS one 2012, 7:e48271.

Millard P, Letisse F, Sokol S, Portais JC: IsoCor: correcting MS data in isotope labeling experiments. Bioinformatics 2012, 28:1294-1296.

Giraudeau P, Cahoreau E, Massou S, Pathan M, Portais JC, Akoka S: UFJCOSY: a fast 3D NMR method for measuring isotopic enrichments in complex samples. Chemphyschem : a European journal of chemical physics and physical chemistry 2012, 13:3098-3101.

Cahoreau E, Peyriga L, Hubert J, Bringaud F, Massou S, Portais JC: Isotopic profiling of (1)(3)C-labeled biological samples by two-dimensional heteronuclear J-resolved nuclear magnetic resonance spectroscopy. Analytical biochemistry 2012, 427:158-163.



 Peyraud R, Schneider K, Kiefer P, Massou S, Vorholt JA, Portais JC: Genome-scale reconstruction and system level investigation of the metabolic network of Methylobacterium extorquens AM1. BMC systems biology 2011, 5:189.

Heux S, Philippe B, Portais JC: High-throughput workflow for monitoring and mining bioprocess data and its application to inferring the physiological response of Escherichia coli to perturbations. Applied and environmental microbiology 2011, 77:7040-7049.

Giraudeau P, Massou S, Robin Y, Cahoreau E, Portais JC, Akoka S: Ultrafast quantitative 2D NMR: an efficient tool for the measurement of specific isotopic enrichments in complex biological mixtures. Analytical chemistry 2011, 83:3112-3119.

Enjalbert B, Jourdan F, Portais JC: Intuitive visualization and analysis of multi-omics data and application to Escherichia coli carbon metabolism. PloS one 2011, 6:e21318.



 Walther T, Novo M, Rossger K, Letisse F, Loret MO, Portais JC, Francois JM: Control of ATP homeostasis during the respiro-fermentative transition in yeast. Molecular systems biology 2010, 6:344.



 Rodriguez-Prados JC, de Atauri P, Maury J, Ortega F, Portais JC, Chassagnole C, Acerenza L, Lindley ND, Cascante M: In silico strategy to rationally engineer metabolite production: A case study for threonine in Escherichia coli. Biotechnology and bioengineering 2009, 103:609-620.

Peyraud R, Kiefer P, Christen P, Massou S, Portais JC, Vorholt JA: Demonstration of the ethylmalonyl-CoA pathway by using 13C metabolomics. Proceedings of the National Academy of Sciences of the United States of America 2009, 106:4846-4851.



 Kiefer P, Portais JC, Vorholt JA: Quantitative metabolome analysis using liquid chromatography-high-resolution mass spectrometry. Analytical biochemistry 2008, 382:94-100.



 van der Werf MJ, Takors R, Smedsgaard J, Nielsen J, Ferenci T, Portais JC, Wittmann C, Hooks M, Tomassini A, Oldiges M, et al: Standard reporting requirements for biological samples in metabolomics experiments: microbial and in vitro biology experiments. Metabolomics : Official journal of the Metabolomic Society 2007, 3:189-194.

Troufflard S, Roscher A, Thomasset B, Barbotin JN, Rawsthorne S, Portais JC: In vivo 13C NMR determines metabolic fluxes and steady state in linseed embryos. Phytochemistry 2007, 68:2341-2350.

Nicolas C, Kiefer P, Letisse F, Kromer J, Massou S, Soucaille P, Wittmann C, Lindley ND, Portais JC: Response of the central metabolism of Escherichia coli to modified expression of the gene encoding the glucose-6-phosphate dehydrogenase. FEBS letters 2007, 581:3771-3776.

Massou S, Nicolas C, Letisse F, Portais JC: NMR-based fluxomics: quantitative 2D NMR methods for isotopomers analysis. Phytochemistry 2007, 68:2330-2340.

Massou S, Nicolas C, Letisse F, Portais JC: Application of 2D-TOCSY NMR to the measurement of specific(13C-enrichments in complex mixtures of 13C-labeled metabolites. Metabolic engineering 2007, 9:252-257.

Kiefer P, Nicolas C, Letisse F, Portais JC: Determination of carbon labeling distribution of intracellular metabolites from single fragment ions by ion chromatography tandem mass spectrometry. Analytical biochemistry 2007, 360:182-188.

Chistoserdova L, Crowther GJ, Vorholt JA, Skovran E, Portais JC, Lidstrom ME: Identification of a fourth formate dehydrogenase in Methylobacterium extorquens AM1 and confirmation of the essential role of formate oxidation in methylotrophy. Journal of bacteriology 2007, 189:9076-9081.

Bolten CJ, Kiefer P, Letisse F, Portais JC, Wittmann C: Sampling for metabolome analysis of microorganisms. Analytical chemistry 2007, 79:3843-3849.