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82 Chen H, Mulder L, Wijma HJ, Wabeke R, Vila Cha Losa JP, Rovetta M, de Leeuw TC, Millias-Argeitis A, Heinemann M (2021) A photo-switchable yeast isocitrate dehydrogenase to control metabolic flux through the citric acid cycle, preprint:

81 Sellner B, Prakapaitė R, van Berkum M, Heinemann M, Harms A, Jenal U (2021) A new sugar for an old phage: A c-di-GMP dependent polysaccharide pathway sensitizes E. coli for bacteriophage infection, mBio, accepted.

80 Vedelaar SR, Radzikowski JL, Heinemann M (2021) A robust method for generating, quantifying and testing large amounts of Escherichia coli persisters, Methods Mol Biol, 2357:41-62., preprint.

79 Yang X, Heinemann M, Howard J, Iyer-Biswas S, Le Treut G, Lynch M, Needleman DJ, Pigolotti S, Rodenfels J, Ronceray P, Shankar S, Tavassoly I, Thutupalli S, Titov DV, Wang J, Foster PJ (2021) Physical Bioenergetics: Energy flows, budget and constraints in cells, PNAS, 118: e2026786118,

78 Alseekh S, Aharoni A, Brotman Y, D’Auria J, Ewald J, Ewald J, Fraser PD, Giavalisco P, Hall RD, Heinemann M, Link H, Luo J, Neumann S, Nielsen J, Perez de Souza L, Saito K, Sauer U, Schroeder FC, Schuster S, Siuzdak G, Skirycz A, Sumner L, Synder M, Tang H, Tohge T, Wen W, Wu S, Xu G, Zamboni N, Fernie AR (2021) Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices, Nature Methods. 18:747-756.

77 Ortega AD, Takhaveev V, Vedelaar S, Long Y, Mestre-Farràs N, Incarnato D, Ersoy F, Olsen LF, Mayer G, Heinemann M (2021) A synthetic RNA-based biosensor for fructose-1,6-bisphosphate that reports glycolytic flux, Cell Chemical Biology, 28:1-15,, preprint.


76 Saldida J, Muntoni AP, de Martino D, Hubmann G, Niebel B, Schmidt AM, Braunstein A, Milias-Argeitis M, Heinemann M (2020) Unbiased metabolic flux inference through combined thermodynamic and 13C flux analysis, preprint.

75 Heinemann M, Basan M, Sauer U (2020) Implications of initial physiological conditions for bacterial adaptation to changing environments. Molecular Systems Biology, 16:e9965 (Correspondance).


74 Monteiro F, Hubmann G, Takhaveev V, Vedelaar S, Norder J, Hekelaar J, Saldida J, Litsios A, Wijma H, Schmidt A, Heinemann M (2019) Measuring glycolytic flux in single yeast cells with an orthogonal biosensor, Molecular Systems Biology, 15: e9071.

73 Zheng Z, Kimkes TEP, Heinemann M (2019) Manipulating rod-shaped bacterial cells with optical tweezers, Scientific Reports, 9: 19086.

72 Kimkes TEP, Heinemann M (2019) How bacteria recognise and respond to surface attachment (review), FEMS Microbiology Reviews, in press.

71 Ozsezen S, Papagiannakis A, Chen H, Niebel B, Milias-Argeitis A, Heinemann M (2019) Inference of the high-level interaction topology between the metabolic and cell cycle oscillators from single-cell dynamics, Cell Systems, 9, 354-365.…)6/j.cels.2019.09.003

70 Litsios A, Huberts DHEW, Terpstra H, Guerra P, Schmidt A, Buczak K, Papagiannakis A, Rovetta M, Hekelaar J, Hubmann G, Exterkate M, Milias-Argeitis A, Heinemann M (2019) Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast, Nature Cell Biology, 21, 1382-1392.…)38/s41556-019-0413-3

69 Leupold S, Hubmann G, Litsios A, Meinema AC, Takhaveev V, Papagiannakis A, Niebel B, Janssens G, Siegel D, Heinemann M (2019) Saccharomyces cerevisiae goes through distinct metabolic phases during its replicative lifespan, eLife, 8:e41046.

68 Balaban NQ, Helaine S, Lewis K, Ackermann M, Aldridge B, Andersson DI, Brynildsen MP, Bumann D, Camilli A, Collins JJ, Dehio C, Fortune S, Ghigo JM, Hardt WD, Harms A, Heinemann M, Hung DT, Jenal U, Levin BR, Michiels J, Storz G, Tan MW, Tenson T, Van Melderen L, Zinkernagel A (2019) Definitions and guidelines for research on antibiotic persistence, Nature Reviews Microbiology, 17, 441-448.…)38/s41579-019-0196-3

67 Yang YS, Kato M, Wu X, Litsios A, Sutter BM, Wang Y, Hsu CH, Wood NE, Lemoff A, Mirzaei H, Heinemann M, Tu BP (2019) Yeast ataxin-2 forms an intracellular condensate required for the inhibition of TORC1 signaling during respiratory growth, Cell, 177: 1-14.…)6/j.cell.2019.02.043

Highlighted in a Commentary by Prouteau and Loewith in Cell Metabolism

66 Niebel B, Leupold KES, Heinemann M (2019) An upper limit in Gibbs energy dissipation governs cellular metabolism, Nature Metabolism, 1: 125-132.…)38/s42255-018-0006-7

Featured in the main Dutch newspaper Trouw
Featured on the Dutch popular science website


65 Kimkes TEP, Heinemann M (2018) Reassessing the role of the Escherichia coli CpxAR system in sensing surface contact, PLoS ONE, 13:e0207181.…)journal.pone.0207181

64 Bley Folly B, Ortega AD, Hubmann G, Bonsing-Vedelaar S, Wijma HJ, van der Meulen P, Milias-Argeitis A, Heinemann M (2018) Assessment of the interaction between the flux-signaling metabolite fructose-1,6-bisphosphate and the bacterial transcription factors CggR and Cra, Molecular Microbiology, 109: 278-290.

Highlighted in a MicroCommentary by Victor de Lorenzo, in Molecular Microbiology

63 Schada von Borzyskowski L, Carrillo M, Leupold KES, Glatter T, Kiefer P, Weishaupt R, Heinemann M, Erb TJ (2018) An engineered Calvin-Benson-Bassham cycle for carbon dioxide fixation in Methylobacterium extorquens AM1, Metabolic Engineering, 47: 423-433.…)/j.ymben.2018.04.003

62 Takhaveev V, Heinemann M (2018) Metabolic heterogeneity in clonal microbial populations (review), Current Opinion in Microbiology, 45: 30-38.…)16/j.mib.2018.02.004

61 Zhang Z, Milias-Argeitis A, Heinemann M (2018) Dynamic single-cell NAD(P)H measurement reveals oscillatory metabolism throughout the E. coli cell division cycle, Scientific Reports, 8: 2162.…)8/s41598-018-20550-7

60 Litsios A, Ortega AD, Heinemann M (2018) Metabolic-flux dependent regulation of microbial physiology (review). Current Opinion in Microbiology, 42: 71-78.…)16/j.mib.2017.10.029


59 Filer D, Thompson MA, Takhaveev V, Dobson AJ, Green JWM, Heinemann M, Tullet JMA, Alic N (2017) Longevity by RNA polymerase III inhibition downstream of TORC1, Nature, 552: 263–267.

Highlighted as “New and Views” in Nature (29.11.2017)
Highlighted in “Papers of Note” in ScienceSignaling(19.12.2017)
“Research Highlight” in Nature Review Molecular Cell Biology (13.12.2017)

58 Heinemann M, Pilpel Y (2017) Editorial overview: Systems biology for biotechnology, Current Opinion in Biotechnology. 46:iv-v.…)j.copbio.2017.07.001

57 Papagiannakis A, de Jonge JJ, Zhang Z, Heinemann M (2017) Quantitative characterization of the auxin-inducible degron: a guide for dynamic protein depletion in single yeast cells, Scientific Reports. 7: 4704.…)8/s41598-017-04791-6

56 Radzikowski JL, Schramke H, Heinemann M (2017) Bacterial persistence from a system-level perspective, Current Opinion in Biotechnology, 46: 98-105.…)j.copbio.2017.02.012

55 Papagiannakis A, Niebel B, Wit EC, Heinemann M (2017) Autonomous metabolic oscillations robustly gate the early and the late cell cycle, Molecular Cell, 65(2): 285-295.…)j.molcel.2016.11.018

2 ‘very good’ recommendations
Highlighted as ‘Principles of Systems Biology’ in Cell Systems
Featured on the Dutch popular science website


54 Radzikowski JL, Vedelaar S, Siegel D, Ortega AD, Schmidt A, Heinemann M (2016) Bacterial persistence is an active σSstress response to metabolic flux limitation. Molecular Systems Biology. 12(9): 882.

53 Haverkorn van Rijsewijk BRB, Kochanowski K, Heinemann M, Sauer U (2016) Distinct transcriptional regulation of the two Escherichia coli transhydrogenases PntAB and UdhA. Microbiology. 162(9): 1672-1679.

52 Schmidt A, Kochanowski K, Vedelaar S, Ahrne E, Volkmer B, Callipo L, Knoops K, Bauer M, Aebersold R, Heinemann M(2016) The quantitative and condition-dependent Escherichia coli proteome. Nature Biotechnology, 34: 104-111.

In the top 5% of all research outputs ever tracked by Altmetric
Highlighted as ‘Research Highlight’ in Nature Methods, 2016
Highly cited paper in the top 1% of the academic field of Biology & Biochemistry (WoS).


51 Janssens G, Meinema A, González J, Wolters K, Schmidt A, Guryev V, Bischoff R, Wit E, Veenhoff L, Heinemann M. (2015) Protein biogenesis machinery is a driver of replicative aging in yeast. eLife. 10.7554/eLife.08527.

In the top 5% of all research outputs ever tracked by Altmetric


50 Daszczuk A, Dessalegne Y, Drenth I, Hendriks E, Jo E, van Lente T, Oldebesten A, Parrish J, Poljakova W, Purwanto A, van Raaphorst R, Boonstra M, van Heel A, Herber M, van der Meulen S, Siebring J, Sorg R, Heinemann M, Kuipers O, Veening JW (2014) Bacillus subtilis biosensor engineered to assess meat spoilage. ACS Synth Biol. 3(12): 999-1002.

49 Huberts DHEW, González J, Lee SS, Litsios A, Hubmann G, Wit E, Heinemann M (2014) Calorie restriction does not elicit a robust extension of replicative lifespan in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States. 111(32): 11727-31.

Highlighted in a commentary in Science News, July 30, 2014
C2W (Koninklijke Nederlandse Chemische Vereniging), 2015

48 Kotte O, Volkmer B, Radzikowski JR, Heinemann M (2014) Phenotypic bistability in Escherichia coli’s central carbon metabolism. Molecular Systems Biology. 10, 736.


47 Huberts DHEW, Janssens GE, Lee SS, Avalos I, Heinemann M (2013) Continuous high-resolution microscopic observation of replicative aging in budding yeast. Journal of Visualized Experiments. 78, e50143, doi:10.3791/50143.

46 Ibanez AJ, Fagerer SR, Schmidt AM, Urban PL, Jefimovs K, Geiger P, Dechant RC, Heinemann M, Zenobi R (2013) Mass spectrometry-based metabolomics of single yeast cells, Proceedings of the National Academy of Sciences of the United States. 110, 8790-8794.

Highlighted as ‘Research Highlight’ in Nature
Mentioned in ‘News and Views” in Nature Chemical Biology

45 Huberts DHEW, Lee SS, Gonzalez J, Janssens GE, Avalos Vizcarra I, Heinemann M (2013) Construction and use of a microfluidic dissection platform for long-term imaging of cellular processes in budding yeast. Nature Protocols. 8, 1019–1027.

Featured on the Nature Protocols web page

44 Gerosa L, Kochanowski K, Heinemann M, Sauer M (2013) Dissecting specific and global transcriptional regulation of bacterial gene expression. Molecular Systems Biology. 9, 658.

43 Zampar GG, Kümmel A, Ewald J, Jol S, Niebel B, Picotti P, Aebersold R, Sauer U, Zamboni N, Heinemann M (2013) Temporal system-level orchestration of the switch from glycolytic to gluconeogenic operation in yeast. Molecular Systems Biology. 9, 651.

42 Kochanowski K, Volkmer B, Gerosa L, Haverkorn van Rijsewijk BR, Schmidt A, Heinemann M (2013) Functioning of a metabolic flux sensor in Escherichia coli. Proceedings of the National Academy of Sciences of the United States. 110, 1130-1135.


41 Adadi R, Volkmer B, Milo R, Heinemann M, Shlomi T (2012) Prediction of microbial growth rate versus biomass yield by a metabolic network with kinetic parameters. PLoS Computational Biology. e1002575.…)journal.pcbi.1002575

40 Schütz R, Zamboni N, Zampieri M, Heinemann M, Sauer U (2012) Multidimensional optimality of microbial metabolism. Science, 336, 601-604.

 1 ‘very good’ recommendation
Highlighted in a commentary in Science
Highly cited paper in the top 1% of the academic field of Biology & Biochemistry (WoS)

39 Lee SS, Avalos Vizcarra I, Huberts DHEW, Lee LP, Heinemann M (2012) Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform. Proceedings of the National Academy of Sciences of the United States, 109: 4916–4920.

2 ‘very good’ recommendations
Highlighted in ‘News & Views’ of Nature
Featured as ‘Research Highlight’ in Nature Methods
Highlighted as ‘Research Highlight’ in Lab-on-a-Chip
Highlighted in the News of the Saccharomyces Genome Database (SGD)

38 Jol SJ, Kümmel A, Terzer M, Stelling J, Heinemann M (2012) System-level insights into yeast metabolism by thermodynamic analysis of elementary flux modes. PLoS Computational Biology, 8: e1002415.…)journal.pcbi.1002415

37 Huberts DHEW, Niebel B, Heinemann M (2012) A flux-sensing mechanism could regulate the switch between respiration and fermentation. FEMS Yeast Research, 12: 118-128.…)67-1364.2011.00767.x


36 Urban PL, Schmidt AM, Fagerer SR, Amantonico A, Ibañez A, Jefimovs K, Heinemann M, Zenobi R (2011) Carbon-13 labelling strategy for studying the ATP metabolism in individual yeast cells by micro-arrays for mass spectrometry. Molecular BioSystems, 7: 2837-2840.

35 Volkmer B, Heinemann M (2011) Condition-dependent cell volume and concentration of Escherichia coli to facilitate data conversion for systems biology modeling. PLoS ONE, 6: e23126.…)journal.pone.0023126

In the top 10% most cited PLoS ONE articles

34 Sturm A, Heinemann M, Arnoldini M, Benecke A, Ackermann M, Benz M, Dormann J, Hardt WD (2011) The cost of virulence: Retarded growth of Salmonella Typhimurium cells expressing type III secretion system 1. PLoS Pathogens, 7: e1002143.…)journal.ppat.1002143

Featured as ‘Research Highlight’ in Nature Reviews Microbiology
In the top 25% most cited PLoS Pathogens articles

33 Bujara M, Schümperli M, Pellaux R, Heinemann M, Panke S (2011) Optimization of a blueprint for in vitro glycolysis by metabolic real-time analysis, Nature Chemical Biology, 7: 271-277.

32 Heinemann M, Sauer U (2011) From good old biochemical analyses to high-throughput omics measurements and back (Editorial), Current Opinion in Biotechnology, 22: 1-2.

31 Heinemann M, Zenobi R (2011) Single cell metabolomics (Review), Current Opinion in Biotechnology, 22: 26-32.…)j.copbio.2010.09.008

30 Costenoble R, Picotti P, Reiter L, Stallmach R, Heinemann M, Sauer U, Aebersold R (2011) Comprehensive quantitative analysis of central carbon and amino acid metabolism in Saccharomyces cerevisiae under multiple conditions. Molecular Systems Biology, 7: 464.


29 Jol SJ, Kümmel A, Hatzimanikatis V, Beard DA, Heinemann M (2010) Thermodynamic calculations for biochemical transport and reaction processes. Biophysical Journal, 99: 3139-3144.…)16/j.bpj.2010.09.043

28 Kümmel A, Ewald JC, Fendt SM, Jol S, Picotti P, Aebersold R, Sauer U, Zamboni N, Heinemann M (2010) Differential glucose repression in common yeast strains in response to a HXK2 deletion. FEMS Yeast Research, 10: 322-332.…)67-1364.2010.00609.x

27 Heinemann M, Sauer U (2010) Systems biology of microbial metabolism (Review). Current Opinion in Microbiology, 13: 337-343.…)16/j.mib.2010.02.005

26 Kotte O, Zaugg JB, Heinemann M (2010) Bacterial adaptation through distributed sensing of metabolic fluxes. Molecular Systems Biology, 6: 355.

Listed in the ‘top ten charts’ of the journal

25 Bujara M, Schümperli M, Billerbeck S, Heinemann M, Panke S (2010) Exploiting cell free systems: Implementation and debugging of a system of biotransformations. Biotechnology and Bioengineering, 106: 376-89.


24 de Graaf AA, Freidig AP, De Roos B, Jamsheedi N, Heinemann M, Rullmann JAC, Hall K, Adiels M, van Ommen B (2009) Nutritional systems biology modeling: from molecular mechanisms to physiology (Review). PLoS Computational Biology, 5, e1000554.…)journal.pcbi.1000554

23 Cook GM, Berney M, Gebhard S, Heinemann M, Cox RA, Danilchanka O, Niederweis M (2009) Physiology of mycobacteria (Review). Advances in Microbial Physiology, 55: 81-184.…)0065-2911(09)05502-7

22 Kotte O, Heinemann M (2009) A divide–and–conquer approach to analyze underdetermined biochemical models. Bioinformatics, 25: 519-525.…)ioinformatics/btp004


21 Herrgård MJ, Swainston N, Dobson P, Dunn WB, Arga KY, Arvas M, Blüthgen N, Borger S, Costenoble R, Heinemann M, Hucka M, Le Novère N, Li P, Liebermeister W, Mo ML, Oliveira AP, Petranovic D, Pettifer S, Simeonidis E, Smallbone K, Spasić I, Weichart D, Brent R, Broomhead DS, Westerhoff HV, Kırdar B, Penttilä M, Klipp E, Palsson BØ, Sauer U, Oliver S G, Mendes P, Nielsen J, Kell DB (2008) A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nature Biotechnology, 26: 1055-1060.

20 Amantonico A, Oh JY, Sobek J, Heinemann M, Zenobi R (2008) Mass spectrometric method for analyzing metabolites in yeast with single cell sensitivity. Angewandte Chemie International Edition, 120(29): 5462-5465.

Featured as ‘Research Highlight’ in Nature Chemistry

19 Zamboni N, Kümmel A, Heinemann M (2008) anNET: a tool for network-embedded thermodynamic analysis of quantitative metabolome data. BMC Bioinformatics, 9: 199.

Highly accessed article


18 Hübscher J, Jansen A, Kotte O, Schaefer J, Majcherczyk PA, Harris LG, Bierbaum G, Heinemann M, Berger-Bächi B (2007) Living with an imperfect cell wall: Compensation of femAB inactivation in Staphylococcus aureus. BMC Genomics, 8: 307.

Highly accessed article

17 Sauer U, Heinemann M, Zamboni N (2007) Getting closer to the whole picture (Perspective article). Science, 316: 550-551.

16 Makart S, Heinemann M, Panke S (2007) Characterization of the AlkS/PalkB-expression system as an efficient tool for the production of recombinant proteins in Escherichia coli fed-batch fermentations. Biotechnology and Bioengineering, 96(2): 326-336.


15 Kümmel A, Panke S, Heinemann M (2006) Systematic assignment of thermodynamic constraints in metabolic networks models. BMC Bioinformatics, 7: 512.

14 Heinemann M, Panke S (2006) Synthetic Biology – Putting engineering into biology (Review). Bioinformatics, 22(22): 2790-2799.

Highly cited paper in the top 1% of the academic field of Computer Science (WoS).

13 Seggewiß J, Becker K, Kotte O, Eisenacher M, Khoschkhoi Yazdi MR, Fischer A, McNamara P, Al Laham N, Proctor R, Peters G, Heinemann M, von Eiff C (2006) Reporter metabolite analysis of transcriptional profiles of a Staphylococcus aureus strain with normal phenotype and its isogenic hemB mutant displaying the small colony variant phenotype. Journal of Bacteriology, 188(2): 7765-7777.

12 Kümmel A, Panke S, Heinemann M (2006) Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data. Molecular Systems Biology, 2:2006.0034

Featured as ‘News & Views’ in Molecular Systems Biology

11 Bechtold M, Makart S, Heinemann M, Panke S (2006) Integrated operation of continuous chromatography and biotransformations for the generic high yield production of fine chemicals. Journal of Biotechnology, 124(1): 146-162.…).jbiotec.2006.01.019

10 Bechtold M, Heinemann M, Panke S (2006) Suitability of teicoplanin-aglycone bonded stationary phase for simulated moving bed enantioseparation of racemic amino acids employing composition-constrained eluents. Journal of Chromatography A, 1113(1-2): 167-176.…)j.chroma.2006.02.007


9 Heinemann M, Kümmel A, Ruinatscha R, Panke S (2005) In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network. Biotechnology and Bioengineering, 92(7): 850-864.

8 Buthe A, Recker T, Heinemann M, Hartmeier W, Büchs J, Ansorge-Schumacher MB (2005) pH-optima in lipase-catalysed esterification. Biocatalysis and Biotransformation, 23(5): 307-314.

7 Heinemann M, Meinberg H, Büchs J, Koß HJ, Ansorge-Schumacher MB (2005) Method for quantitative determination of spatial polymer distribution in alginate beads using Raman spectroscopy. Applied Spectroscopy, 59(3): 280-285.

6 Trivedi A, Heinemann M, Spiess AC, Daußmann T, Büchs J (2005) Optimization of adsorptive immobilization of alcohol dehydrogenases. Journal of Bioscience and Bioengineering, 99(4): 340-347.


5 Heinemann M, Limper U, Büchs J (2004) New insights in the spatially resolved dynamic pH measurement in macroscopic large absorbent particles by confocal laser scanning microscopy. Journal of Chromatography A, 1024(1-2): 45-53.…)j.chroma.2003.09.065

4 Ferloni C, Heinemann M, Hummel W, Daußmann T, Büchs J (2004) Optimization of enzymatic gas phase reactions by increasing the long-term stability of the catalyst. Biotechnology Progress, 20(3): 975-978.


3 Heinemann M, Kümmel A, Giesen R, Ansorge-Schumacher MB, Büchs J (2003) Experimental and theoretical analysis of phase equilibria in a two-phase system used for biocatalyzed esterifications. Biocatalysis and Biotransformation, 21(3): 115-121.…)/1024242031000155082


2 Doumèche B, Heinemann M, Büchs J, Hartmeier W, Ansorge-Schumacher MB (2002) Enzymatic catalysis in gel-stabilized two-phase systems: Improvement of the solvent phase. Journal of Molecular Catalysis B: Enzymatic, 18(1-3): 19-27.…)1381-1177(02)00044-9

1 Heinemann M, Wagner T, Doumèche B, Ansorge-Schumacher MB, Büchs J (2002) A new approach for the spatially resolved qualitative analysis of the protein distribution in hydrogel beads based on confocal laser scanning microscopy. Biotechnology Letters, 24(10): 845-850.