METASYS Articles


Bergès, C., Cahoreau, E., Millard, P., Enjalbert, B., Dinclaux, M., Heuillet, M., Kulyk, H., Gales, L., Butin, N., Chazalviel, M., Palama, T., Guionnet, M., Sokol, S., Peyriga, L., Bellvert, F., Heux, S., Portais, J.-C. 2021. Exploring the Glucose Fluxotype of the E. coli y-ome Using High-Resolution Fluxomics. Metabolites. 11, 271.


Cox N., Millard P., Charlier C., Lippens G. 2021. Improved NMR detection of phospho-metabolites in a complex mixture. Analytical chemistry, 93, 11, 4818– 4824.


Millard P., Enjalbert B., Uttenweiler-Joseph S., Portais J.C., Létisse F. 2021. Control and regulation of acetate overflow in Escherichia coli. eLife. doi: 10.7554/eLife.63661


Millard P., Sokol S., Kohlstedt M., Wittmann C., Letisse F., Lippens G. Portais J.C. 2021. IsoSolve: an integrative framework to improve isotopic coverage and consolidate isotopic measurements by MS and/or NMR. Anal. Chem. 93, 27, 9428–9436.


Millard P, Pérochon J, Létisse F. 2021. Functional Analysis of Deoxyhexose Sugar Utilization in Escherichia coli Reveals Fermentative Metabolism under Aerobic Conditions. Appl. Environ. Microbiol., 2021, doi: 10.1128/AEM.00719-21.


Wendisch VF, Kosec G, Heux S, Brautaset T. 2021. Aerobic Utilization of Methanol for Microbial Growth and Production. Adv. Biochem. Eng. Biotechnol. DOI : 10.1007/10_2021_177


Pelus A, Bordes G, Barbe S, Bouchiba Y, Burnard C, Cortés J, Enjalbert B, Esque J, Estaña A, Fauré R, Henras AK, Heux S, Le Men C, Millard P, Nouaille S, Pérochon J, Toanen M, Truan G, Verdier A, Wagner C, Romeo Y, Montanier CY. 2021. A tripartite carbohydrate-binding module to functionalize cellulose nanocrystals. Biomater Sci.,9(22):7444-7455.


Brito LF, Irla M, Nærdal I, Le SB, Delépine B, Heux S, Brautaset T. 2021. Evaluation of Heterologous Biosynthetic Pathways for Methanol-Based 5-Aminovalerate Production by Thermophilic Bacillus methanolicus. Front. Bioeng. Biotechnol., 9:686319.


Clément Patacq, Nicolas Chaudet and Fabien Letisse. Crucial role of ppGpp in the resilience of Escherichia coli to growth disruption. mSphere, 2020 Dec 23;5(6):e01132-20. doi: 10.1128/mSphere.01132-20. 10.1128/mSphere.01132-20


Young-Kyoung Park, Florence Bordes, Fabien Létisse and Jean-Marc Nicaud. Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica. Metabolic Engineering Communications, 2020 Dec 19;12:e00158. doi: 10.1016/j.mec.2020.e00158. eCollection 2021 Jun. 10.1016/j.mec.2020.e00158


De Simone, A., Vicente, C. M., Peiro, C., Gales, L., Bellvert, F., Enjalbert, B., & Heux, S. (2020). Mixing and matching methylotrophic enzymes to design a novel methanol utilization pathway in E. coli. Metabolic Engineering, 61, 315‑325.


Delépine, B., López, M. G., Carnicer, M., Vicente, C., Wendisch, V., & Heux, S. (2020). Charting the Metabolic Landscape of the Facultative Methylotroph Bacillus methanolicus. mSystems, 5(5).


Dellero, Y., Heulliet, M., Marnet, N., Bellvert, F., Millard, P., & Bouchereau, A. (2020). Sink/Source Balance of Leaves Influences Amino Acid Pools and Their Associated Metabolic Fluxes in Winter Oilseed Rape (Brassica napus L.). Metabolites, 10(4), 150.


Haupka, C., Delépine, B., Irla, M., Heux, S., & Wendisch, V. F. (2020). Flux Enforcement for Fermentative Production of 5-Aminovalerate and Glutarate by Corynebacterium glutamicum. Catalysts, 10(9).


Hennig, G., Haupka, C., Brito, L. F., Rückert, C., Cahoreau, E., Heux, S., & Wendisch, V. F. (2020). Methanol-Essential Growth of Corynebacterium glutamicum : Adaptive Laboratory Evolution Overcomes Limitation due to Methanethiol Assimilation Pathway. International Journal of Molecular Sciences, 21(10).


Heuillet, M., Millard, P., Cissé, M. Y., Linares, L. K., Létisse, F., Manié, S., Le Cam, L., Portais, J.-C., & Bellvert, F. (2020). Simultaneous Measurement of Metabolite Concentration and Isotope Incorporation by Mass Spectrometry. Analytical Chemistry, 92(8), 5890‑5896.


Millard, P., Schmitt, U., Kiefer, P., Vorholt, J. A., Heux, S., & Portais, J.-C. (2020). ScalaFlux : A scalable approach to quantify fluxes in metabolic subnetworks. PLoS Computational Biology, 16(4).


Wang Z, Tauzin AS, Laville E, Tedesco P, Létisse F, Terrapon N, Lepercq P, Mercade M, Potocki-Veronese G. (2020). Harvesting of Prebiotic Fructooligosaccharides by Nonbeneficial Human Gut Bacteria | mSphere ( ). mSphere, 5(1):e00771-19. doi: 10.1128/mSphere.00771-19


Dinclaux M, Cahoreau E, Millard P, Létisse F, Lippens G. (2020). Increasing field strength versus advanced isotope labeling for NMR-based fluxomics. Magn Reson Chem., 58(4):305-311. doi: 10.1002/mrc.4988


Millard, P., Schmitt, U., Kiefer, P., Vorholt, J.A., Heux, S., Portais, J.C. [2019] "ScalaFlux: a scalable approach to quantify fluxes in metabolic subnetworks". BioRxiv, DOI: 10.1101/735308


Castano-Cerezo, S., Kulyk-Barbier, H., Millard, P., Portais, J.C., Heux, S., Truan, G., Bellvert, F. [2019]. "Functional analysis of isoprenoid precursors biosynthesis by quantitative metabolomics and isotopologue profiling". Metabolomics, DOI: 10.1007/s11306-019-1580-8


Cox, N., Kuemmerle, R., Millard, P., Cahoreau, E., Francois, J. M., Parrou, J. L. and Lippens, G. (2019). "Integrated pH Measurement during Reaction Monitoring with Dual-Reception (1)H-(31)P NMR Spectroscopy."  91(6): 3959-3963. Anal. Chem.


Millard, P., Delepine, B., Guionnet, M., Heuillet, M., Bellvert, F. and Letisse, F. (2019). "IsoCor: isotope correction for high-resolution MS labeling experiments." Bioinformatics.


Millard, P. and Lippens, G. (2019). "Automated analysis of protein-ligand interactions by 2D NMR." bioRxiv preprint.


Peiro, P., Millard, P., de Simone, A., Cahoreau, E., Peyriga, L., Enjalbert, B. and S., H. (2019). "Chemical and metabolic controls on dihydroxyacetone metabolism lead to a suboptimal growth of E. coli." Appl. Environ. Microbiol.



Cottret, L., Frainay, C., Chazalviel, M., Cabanettes, F., Gloaguen, Y., Camenen, E., Merlet, B., Heux, S., Portais, J. C., Poupin, N., Vinson, F. and Jourdan, F. (2018). "MetExplore: collaborative edition and exploration of metabolic networks."  46(W1): W495-W502. Nucleic Acids Res.


Heuillet, M., Bellvert, F., Cahoreau, E., Letisse, F., Millard, P. and Portais, J. C. (2018). "Methodology for the Validation of Isotopic Analyses by Mass Spectrometry in Stable-Isotope Labeling Experiments."  90(3): 1852-1860. Anal. Chem.


Heux S., Brautaset T., Vorholt J.A., Wendisch V.F. and J.C., P. (2018). Synthetic Methylotrophy: Past, Present, and Future. Methane Biocatalysis: Paving the Way to Sustainability. Kalyuzhnaya M. and X. XH., Springer, Cham.


Lippens, G., Cahoreau, E., Millard, P., Charlier, C., Lopez, J., Hanoulle, X. and Portais, J. C. (2018). "In-cell NMR: from metabolites to macromolecules."  143(3): 620-629. Analyst.


Patacq, C., Chaudet, N. and Letisse, F. (2018). "Absolute Quantification of ppGpp and pppGpp by Double-Spike Isotope Dilution Ion Chromatography-High-Resolution Mass Spectrometry."  90(18): 10715-10723. Anal. Chem.


Quedeville, V., Ouazaite, H., Polizzi, B., Fox, R. O., Villedieu, P., Fede, P., Letisse, F. and Morchain, J. (2018). "A two-dimensional population balance model for cell growth including multiple uptake systems.". Chemical Engineering Research and Design.


Sinnaeve, D., Dinclaux, M., Cahoreau, E., Millard, P., Portais, J. C., Letisse, F. and Lippens, G. (2018). "Improved Isotopic Profiling by Pure Shift Heteronuclear 2D J-Resolved NMR Spectroscopy."  90(6): 4025-4031. Anal. Chem.


Stuani, L., Riols, F., Millard, P., Sabatier, M., Batut, A., Saland, E., Viars, F., Tonini, L., Zaghdoudi, S., Linares, L. K., Portais, J. C., Sarry, J. E. and Bertrand-Michel, J. (2018). "Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia."  19(11). Int. J. Mol. Sci.


Trichez, D., Auriol, C., Baylac, A., Irague, R., Dressaire, C., Carnicer-Heras, M., Heux, S., Francois, J. M. and Walther, T. (2018). "Engineering of Escherichia coli for Krebs cycle-dependent production of malic acid."  17(1): 113. Microb. Cell. Fact.



Angles, F., Castanie-Cornet, M. P., Slama, N., Dinclaux, M., Cirinesi, A. M., Portais, J. C., Letisse, F. and Genevaux, P. (2017). "Multilevel interaction of the DnaK/DnaJ(HSP70/HSP40) stress-responsive chaperone machine with the central metabolism."  7: 41341. Sci Rep.


Enjalbert, B., Millard, P., Dinclaux, M., Portais, J. C. and Letisse, F. (2017). "Acetate fluxes in Escherichia coli are determined by the thermodynamic control of the Pta-AckA pathway."  7: 42135. Sci Rep.


Heux, S., Berges, C., Millard, P., Portais, J. C. and Letisse, F. (2017). "Recent advances in high-throughput 13C-fluxomics."  43: 104-109. Curr. Opin. Biotechnol.


Letoffe, S., Chalabaev, S., Dugay, J., Stressmann, F., Audrain, B., Portais, J. C., Letisse, F. and Ghigo, J. M. (2017). "Biofilm microenvironment induces a widespread adaptive amino-acid fermentation pathway conferring strong fitness advantage in Escherichia coli."  13(5): e1006800. PLoS Genet.


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


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


Morin, M., Ropers, D., Cinquemani, E., Portais, J. C., Enjalbert, B. and Cocaign-Bousquet, M. (2017). "The Csr System Regulates Escherichia coli Fitness by Controlling Glycogen Accumulation and Energy Levels."  8(5). mBio.

Rodriguez, A., Martinez, J. A., Millard, P., Gosset, G., Portais, J. C., Letisse, F. and Bolivar, F. (2017). "Plasmid-encoded biosynthetic genes alleviate metabolic disadvantages while increasing glucose conversion to shikimate in an engineered Escherichia coli strain."  114(6): 1319-1330. Biotechnol. Bioeng.


Schatschneider, S., Schneider, J., Blom, J., Letisse, F., Niehaus, K., Goesmann, A. and Vorholter, F. J. (2017). "Systems and synthetic biology perspective of the versatile plant-pathogenic and polysaccharide-producing bacterium Xanthomonas campestris."  163(8): 1117-1144. Microbiology.



Carnicer, M., Vieira, G., Brautaset, T., Portais, J. C. and Heux, S. (2016). "Quantitative metabolomics of the thermophilic methylotroph Bacillus methanolicus."  15: 92. Microb. Cell. Fact.


Morin, M., Ropers, D., Letisse, F., Laguerre, S., Portais, J. C., Cocaign-Bousquet, M. and Enjalbert, B. (2016). "The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli."  100(4): 686-700. Mol. Microbiol.


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. and Bordes, F. (2016). "Functional characterization of a gene locus from an uncultured gut Bacteroides conferring xylo-oligosaccharides utilization to Escherichia coli."  102(4): 579-592. Mol. Microbiol.


Treitz, C., Enjalbert, B., Portais, J. C., Letisse, F. and Tholey, A. (2016). "Differential quantitative proteome analysis of Escherichia coli grown on acetate versus glucose."  16(21): 2742-2746. Proteomics.




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


Enjalbert, B., Cocaign-Bousquet, M., Portais, J. C. and Letisse, F. (2015). "Acetate Exposure Determines the Diauxic Behavior of Escherichia coli during the Glucose-Acetate Transition."  197(19): 3173-3181. J. Bacteriol.


Heux, S., Meynial-Salles, I., O'Donohue, M. J. and Dumon, C. (2015). "White biotechnology: state of the art strategies for the development of biocatalysts for biorefining." Biotechnol. Adv.


Lessmeier, L., Pfeifenschneider, J., Carnicer, M., Heux, S., Portais, J. C. and Wendisch, V. F. (2015). "Production of carbon-13-labeled cadaverine by engineered Corynebacterium glutamicum using carbon-13-labeled methanol as co-substrate." Appl. Microbiol. Biotechnol.


Millard, P., Portais, J. C. and Mendes, P. (2015). "Impact of kinetic isotope effects in isotopic studies of metabolic systems."  9: 64. BMC Syst. Biol.


Muller, J. E., Meyer, F., Litsanov, B., Kiefer, P., Potthoff, E., Heux, S., Quax, W. J., Wendisch, V. F., Brautaset, T., Portais, J. C. and Vorholt, J. A. (2015). "Engineering Escherichia coli for methanol conversion."  28: 190-201. Metab. Eng.


Sokol, S. and Portais, J. C. (2015). "Theoretical Basis for Dynamic Label Propagation in Stationary Metabolic Networks under Step and Periodic Inputs."  10(12): e0144652. PLoS One.


Stanford, N. J., Millard, P. and Swainston, N. (2015). "RobOKoD: microbial strain design for (over)production of target compounds."  3: 17. Front Cell Dev Biol.



Heux, S., Poinot, J., Massou, S., Sokol, S. and Portais, J. C. (2014). "A novel platform for automated high-throughput fluxome profiling of metabolic variants."  25: 8-19. Metab. Eng.


Millard, P., Letisse, F., Sokol, S. and Portais, J. C. (2014). "Correction of MS data for naturally occurring isotopes in isotope labelling experiments."  1191: 197-207. Methods Mol Biol.


Millard, P., Massou, S., Portais, J. C. and Letisse, F. (2014). "Isotopic studies of metabolic systems by mass spectrometry: using Pascal's triangle to produce biological standards with fully controlled labeling patterns."  86(20): 10288-10295. Anal. Chem.


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


Millard, P., Sokol, S., Letisse, F. and Portais, J. C. (2014). "IsoDesign: a software for optimizing the design of 13C-metabolic flux analysis experiments."  111(1): 202-208. Biotechnol. Bioeng.


Silva, R. R., Jourdan, F., Salvanha, D. M., Letisse, F., Jamin, E. L., Guidetti-Gonzalez, S., Labate, C. A. and Vencio, R. Z. (2014). "ProbMetab: an R package for Bayesian probabilistic annotation of LC-MS-based metabolomics."  30(9): 1336-1337. Bioinformatics.


Vieira, G., Carnicer, M., Portais, J. C. and Heux, S. (2014). "FindPath: a Matlab solution for in silico design of synthetic metabolic pathways."  30(20): 2986-2988. Bioinformatics.



Boisseau, R., Charrier, B., Massou, S., Portais, J. C., Akoka, S. and Giraudeau, P. (2013). "Fast spatially encoded 3D NMR strategies for (13)C-based metabolic flux analysis."  85(20): 9751-9757. Anal. Chem.


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


Revelles, O., Millard, P., Nougayrede, J. P., Dobrindt, U., Oswald, E., Letisse, F. and Portais, J. C. (2013). "The carbon storage regulator (Csr) system exerts a nutrient-specific control over central metabolism in Escherichia coli strain Nissle 1917."  8(6): e66386. PLoS One.


Xu, Y. F., Letisse, F., Absalan, F., Lu, W., Kuznetsova, E., Brown, G., Caudy, A. A., Yakunin, A. F., Broach, J. R. and Rabinowitz, J. D. (2013). "Nucleotide degradation and ribose salvage in yeast."  9: 665. Mol. Syst. Biol.




Cahoreau, E., Peyriga, L., Hubert, J., Bringaud, F., Massou, S. and Portais, J. C. (2012). "Isotopic profiling of (1)(3)C-labeled biological samples by two-dimensional heteronuclear J-resolved nuclear magnetic resonance spectroscopy."  427(2): 158-163. Anal. Biochem.


Giraudeau, P., Cahoreau, E., Massou, S., Pathan, M., Portais, J. C. and Akoka, S. (2012). "UFJCOSY: a fast 3D NMR method for measuring isotopic enrichments in complex samples."  13(13): 3098-3101. ChemPhysChem.


Millard, P., Letisse, F., Sokol, S. and Portais, J. C. (2012). "IsoCor: correcting MS data in isotope labeling experiments."  28(9): 1294-1296. Bioinformatics.


Peyraud, R., Kiefer, P., Christen, P., Portais, J. C. and Vorholt, J. A. (2012). "Co-consumption of methanol and succinate by Methylobacterium extorquens AM1."  7(11): e48271. PLoS One.


Schneider, K., Peyraud, R., Kiefer, P., Christen, P., Delmotte, N., Massou, S., Portais, J. C. and Vorholt, J. A. (2012). "The ethylmalonyl-CoA pathway is used in place of the glyoxylate cycle by Methylobacterium extorquens AM1 during growth on acetate."  287(1): 757-766. J. Biol. Chem.


Sokol, S., Millard, P. and Portais, J. C. (2012). "influx_s: increasing numerical stability and precision for metabolic flux analysis in isotope labelling experiments."  28(5): 687-693. Bioinformatics.



Enjalbert, B., Jourdan, F. and Portais, J. C. (2011). "Intuitive visualization and analysis of multi-omics data and application to Escherichia coli carbon metabolism."  6(6): e21318. PLoS One.


Giraudeau, P., Massou, S., Robin, Y., Cahoreau, E., Portais, J. C. and Akoka, S. (2011). "Ultrafast quantitative 2D NMR: an efficient tool for the measurement of specific isotopic enrichments in complex biological mixtures."  83(8): 3112-3119. Anal. Chem.


Heux, S., Philippe, B. and Portais, J. C. (2011). "High-throughput workflow for monitoring and mining bioprocess data and its application to inferring the physiological response of Escherichia coli to perturbations."  77(19): 7040-7049. Appl. Environ. Microbiol.


Peyraud, R., Schneider, K., Kiefer, P., Massou, S., Vorholt, J. A. and Portais, J. C. (2011). "Genome-scale reconstruction and system level investigation of the metabolic network of Methylobacterium extorquens AM1."  5: 189. BMC Syst. Biol.



Peyraud, R., Kiefer, P., Christen, P., Massou, S., Portais, J. C. and Vorholt, J. A. (2009). "Demonstration of the ethylmalonyl-CoA pathway by using 13C metabolomics."  106(12): 4846-4851. Proc. Natl. Acad. Sci. U. S. A.


Rodriguez-Prados, J. C., de Atauri, P., Maury, J., Ortega, F., Portais, J. C., Chassagnole, C., Acerenza, L., Lindley, N. D. and Cascante, M. (2009). "In silico strategy to rationally engineer metabolite production: A case study for threonine in Escherichia coli."  103(3): 609-620. Biotechnol. Bioeng.


Walther, T., Novo, M., Rossger, K., Letisse, F., Loret, M. O., Portais, J. C. and Francois, J. M. (2010). "Control of ATP homeostasis during the respiro-fermentative transition in yeast."  6: 344. Mol. Syst. Biol.




Kiefer, P., Portais, J. C. and Vorholt, J. A. (2008). "Quantitative metabolome analysis using liquid chromatography-high-resolution mass spectrometry."  382(2): 94-100. Anal. Biochem.




Bolten, C. J., Kiefer, P., Letisse, F., Portais, J. C. and Wittmann, C. (2007). "Sampling for metabolome analysis of microorganisms."  79(10): 3843-3849. Anal. Chem.


Chistoserdova, L., Crowther, G. J., Vorholt, J. A., Skovran, E., Portais, J. C. and Lidstrom, M. E. (2007). "Identification of a fourth formate dehydrogenase in Methylobacterium extorquens AM1 and confirmation of the essential role of formate oxidation in methylotrophy."  189(24): 9076-9081. J. Bacteriol.


Kiefer, P., Nicolas, C., Letisse, F. and Portais, J. C. (2007). "Determination of carbon labeling distribution of intracellular metabolites from single fragment ions by ion chromatography tandem mass spectrometry."  360(2): 182-188. Anal. Biochem.


Massou, S., Nicolas, C., Letisse, F. and Portais, J. C. (2007). "Application of 2D-TOCSY NMR to the measurement of specific(13C-enrichments in complex mixtures of 13C-labeled metabolites."  9(3): 252-257. Metab. Eng.


Massou, S., Nicolas, C., Letisse, F. and Portais, J. C. (2007). "NMR-based fluxomics: quantitative 2D NMR methods for isotopomers analysis."  68(16-18): 2330-2340. Phytochemistry.


Nicolas, C., Kiefer, P., Letisse, F., Kromer, J., Massou, S., Soucaille, P., Wittmann, C., Lindley, N. D. and Portais, J. C. (2007). "Response of the central metabolism of Escherichia coli to modified expression of the gene encoding the glucose-6-phosphate dehydrogenase."  581(20): 3771-3776. FEBS Lett.


Troufflard, S., Roscher, A., Thomasset, B., Barbotin, J. N., Rawsthorne, S. and Portais, J. C. (2007). "In vivo 13C NMR determines metabolic fluxes and steady state in linseed embryos."  68(16-18): 2341-2350. Phytochemistry.