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Enzyme Cascade Kinetic Modelling

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Enzyme Cascade Design and Modelling

Abstract

Cascade multi-step reactions have gained a lot of attention in the last decade due to their numerous advantages against traditional organic synthesis methods. Indeed, they are excellent from the viewpoint of sustainability. Nevertheless, one has to bear in mind that as the number of enzymes and compounds increases, the number of dependencies between different variables also increases. For such complex systems to work, and to become fully applicable on larger scale, it is important to understand them from within, i.e., from the viewpoint of reaction engineering. The path towards development of these complex processes can be challenging, with many open questions, but with the aid of modelling all the numerous interdependencies can be described and understood. Using models, reactions can be optimized faster and at low cost. This chapter presents the methodology for the multi-step process development via kinetic modelling, with challenges and problems addressed, and potential solutions offered.

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Abbreviations

BP :

Biocatalyst productivity [kgproduct kgbiocatalyst−1]

c :

Molar concentration [mM]

v :

Mass concentration [g L−1]

K i :

Inhibition constant [mM]

K M :

Michaelis constant [mM]

Q P :

Volumetric productivity [g L−1 h−1]

r :

Reaction rate [mM min−1]

V max :

Maximum reaction rate [U mg−1]

Y product :

Product yield [%]

References

  1. Liese A, Seelbach K, Wandrey C (2006) Industrial biotransformations, 2nd edn. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

    Book  Google Scholar 

  2. Gurung N, Ray S, Bose S, Rai V (2013) A broader view: microbial enzymes and their relevance in industries, medicine, and beyond. BioMed Res Int 2013:329121

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Fessner W-D (2005) What is the color of YOUR biocatalysis? Adv Synth Catal 347(7–8):903–904

    Article  CAS  Google Scholar 

  4. Bommarius AS, Riebel BR (2004) Biocatalysis: fundamentals and applications. WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

    Book  Google Scholar 

  5. Fessner WD (2015) Systems biocatalysis: development and engineering of cell-free “artificial metabolisms” for preparative multi-enzymatic synthesis. New Biotechnol 32(6):658–664

    Article  CAS  Google Scholar 

  6. Tessaro D, Pollegioni L, Piubelli L, D’Arrigo P, Servi S (2015) Systems biocatalysis: an artificial metabolism for interconversion of functional groups. ACS Catal 5(3):1604–1608

    Article  CAS  Google Scholar 

  7. Woodley JM (2018) Integrating protein engineering with process design for biocatalysis. Philos Trans A Math Phys Eng Sci 376(2110):20170062

    PubMed  Google Scholar 

  8. Hammer SC, Knight AM, Arnold FH (2017) Design and evolution of enzymes for non-natural chemistry. Curr Opin Green Sustain Chem 7:23–30

    Article  Google Scholar 

  9. Schrittwieser JH, Velikogne S, Hall M, Kroutil W (2018) Artificial biocatalytic linear cascades for preparation of organic molecules. Chem Rev 118(1):270–348

    Article  CAS  PubMed  Google Scholar 

  10. Schmidt S, Castiglione K, Kourist R (2018) Overcoming the incompatibility challenge in chemoenzymatic and multi-catalytic cascade reactions. Chem Eur J 24(8):1755–1768

    Article  CAS  PubMed  Google Scholar 

  11. Findrik Z, Vasić-Rački Đ (2009) Overview on reactions with multi-enzyme systems. Chem Biochem Eng Q 23(4):545–553

    CAS  Google Scholar 

  12. Sperl JM, Sieber V (2018) Multienzyme cascade reactions—status and recent advances. ACS Catal 8(3):2385–2396

    Article  CAS  Google Scholar 

  13. Xue R, Woodley JM (2012) Process technology for multi-enzymatic reaction systems. Bioresour Technol 115:183–195

    Article  CAS  PubMed  Google Scholar 

  14. Riva S, Fessner W-D (2014) Cascade biocatalysis. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

    Book  Google Scholar 

  15. Vasić-Rački Đ, Findrik Z, Vrsalović Presečki A (2011) Modelling as a tool of enzyme reaction engineering for enzyme reactor development. Appl Microbiol Biotechnol 91(4):845–856

    Article  PubMed  CAS  Google Scholar 

  16. Ringborg RH, Woodley JM (2016) The application of reaction engineering to biocatalysis. React Chem Eng 1(1):10–22

    Article  CAS  Google Scholar 

  17. Tufvesson P, Lima-Ramos J, Haque NA, Gernaey KV, Woodley JM (2013) Advances in the process development of biocatalytic processes. Org Process Res Dev 17(10):1233–1238

    Article  CAS  Google Scholar 

  18. Sheldon RA, Pereira PC (2017) Biocatalysis engineering: the big picture. Chem Soc Rev 46(10):2678–2691

    Article  CAS  PubMed  Google Scholar 

  19. Sheldon RA, Woodley JM (2018) Role of biocatalysis in sustainable chemistry. Chem Rev 118(2):801–838

    Article  CAS  PubMed  Google Scholar 

  20. Heiden S, Eiden F, Woodley JM, Schmid A (2014) ChemBioTec – linking chemistry, biology and engineering. J Mol Catal B: Enzym 103:1

    Article  CAS  Google Scholar 

  21. Smith MEB, Chen BH, Hibbert EG, Kaulmann U, Smithies K, Galman JL et al (2010) A multidisciplinary approach toward the rapid and preparative-scale biocatalytic synthesis of chiral amino alcohols: a concise transketolase-/ω-transaminase-mediated synthesis of (2S,3S)-2-aminopentane-1,3-diol. Org Process Res Dev 14(1):99–107

    Google Scholar 

  22. Wagner N, Bosshart A, Wahler S, Failmezger J, Panke S, Bechtold M (2015) Model-based cost optimization of a reaction–separation integrated process for the enzymatic production of the rare sugar D-psicose at elevated temperatures. Chem Eng Sci 137:423–435

    Article  CAS  Google Scholar 

  23. Heitzig M, Linninger AA, Sin G, Gani R (2014) A computer-aided framework for development, identification and management of physiologically-based pharmacokinetic models. Comput Chem Eng 71:677–698

    Article  CAS  Google Scholar 

  24. Santacoloma PA, Sin G, Gernaey KV, Woodley JM (2011) Multienzyme-catalyzed processes: next-generation biocatalysis. Org Process Res Dev 15(1):203–212

    Google Scholar 

  25. Leuchs S, Lima-Ramos J, Greiner L, Al-Haque N, Tufvesson P, Woodley JM (2013) Reaction engineering of biocatalytic enantioselective reduction: a case study for aliphatic ketones. Org Process Res Dev 17(8):1027–1035

    Article  CAS  Google Scholar 

  26. Zhang G, Quin MB, Schmidt-Dannert C (2018) Self-assembling protein scaffold system for easy in vitro coimmobilization of biocatalytic cascade enzymes. ACS Catal 8(6):5611–5620

    Article  CAS  Google Scholar 

  27. Kirk-Othmer encyclopedia of chemical technology, 5th edn. Wiley-Interscience, Hoboken (2004)

    Google Scholar 

  28. Petrides DP, Koulouris A, Lagonikos PT (2002) The role of process simulation in pharmaceutical process development and product commercialization. Pharm Eng 22(1):56–65

    Google Scholar 

  29. Sudar M, Vasić-Rački Đ, Müller M, Walter A, Findrik Blažević Z (2018) Mathematical model of the MenD-catalyzed 1,4-addition (Stetter reaction) of alpha-ketoglutaric acid to acrylonitrile. J Biotechnol 268:71–80

    Google Scholar 

  30. Sudar M, Findrik Z, Vuković Domanovac M, Vasić-Rački Đ (2014) Coenzyme regeneration catalyzed by NADH oxidase from Lactococcus lactis. Biochem Eng J 88:12–18

    Google Scholar 

  31. Zhang Y, Wang Q, Hess H (2017) Increasing enzyme cascade throughput by pH-engineering the microenvironment of individual enzymes. ACS Catal 7(3):2047–2051

    Article  CAS  Google Scholar 

  32. Wang B, Land H, Berglund P (2013) An efficient single-enzymatic cascade for asymmetric synthesis of chiral amines catalyzed by omega-transaminase. Chem Commun (Camb) 49(2):161–163

    Article  CAS  Google Scholar 

  33. Ardao I, Zeng A-P (2013) In silico evaluation of a complex multi-enzymatic system using one-pot and modular approaches: application to the high-yield production of hydrogen from a synthetic metabolic pathway. Chem Eng Sci 87:183–193

    Article  CAS  Google Scholar 

  34. Schmidt S, Büchsenschütz HC, Scherkus C, Liese A, Gröger H, Bornscheuer UT (2015) Biocatalytic access to chiral polyesters by an artificial enzyme cascade synthesis. ChemCatChem 7(23):3951–3955

    Article  CAS  Google Scholar 

  35. Sudar M, Findrik Z, Vasić-Rački Đ, Soler A, Clapés P (2015) A new concept for production of (3S,4R)-6-[(benzyloxycarbonyl)amino]-5,6-dideoxyhex-2-ulose, a precursor of D-fagomine. RSC Adv 5(85):69819–69828

    Article  CAS  Google Scholar 

  36. Gomez Baraibar A, Reichert D, Mugge C, Seger S, Groger H, Kourist R (2016) A one-pot cascade reaction combining an encapsulated decarboxylase with a metathesis catalyst for the synthesis of bio-based antioxidants. Angew Chem Int Ed Engl 55(47):14823–14827

    Article  CAS  PubMed  Google Scholar 

  37. Rios-Lombardia N, Vidal C, Liardo E, Moris F, Garcia-Alvarez J, Gonzalez-Sabin J (2016) From a sequential to a concurrent reaction in aqueous medium: ruthenium-catalyzed allylic alcohol isomerization and asymmetric bioreduction. Angew Chem Int Ed Engl 55(30):8691–8695

    Article  CAS  PubMed  Google Scholar 

  38. Fidaleo M, Lavecchia R (2003) Kinetic study of enzymatic urea hydrolysis in the pH range 4–9. Chem Biochem Eng Q 17(4):311–318

    CAS  Google Scholar 

  39. Wang S, Meng X, Zhou H, Liu Y, Secundo F, Liu Y (2016) Enzyme stability and activity in non-aqueous reaction systems: a mini review. Catalysts 6(2):32

    Article  CAS  Google Scholar 

  40. Klibanov AM (1997) Why are enzymes less active in organic solvents than in water? Trends Biotechnol 15(3):97–101

    Article  CAS  PubMed  Google Scholar 

  41. Sudar M, Findrik Z, Vasić-Rački Đ, Clapés P, Lozano C (2013) Aldol addition of dihydroxyacetone to N-Cbz-3-aminopropanal catalyzed by two aldolases variants in microreactors. Enzyme Microb Technol 53(1):38–45

    Article  CAS  PubMed  Google Scholar 

  42. Zhong C, Wei P, Zhang Y-HP (2017) A kinetic model of one-pot rapid biotransformation of cellobiose from sucrose catalyzed by three thermophilic enzymes. Chem Eng Sci 161:159–166

    Article  CAS  Google Scholar 

  43. Burda E, Hummel W, Groger H (2008) Modular chemoenzymatic one-pot syntheses in aqueous media: combination of a palladium-catalyzed cross-coupling with an asymmetric biotransformation. Angew Chem Int Ed Engl 47(49):9551–9554

    Article  CAS  PubMed  Google Scholar 

  44. Charmantray F, Dellis P, Samreth S, Hecquet L (2006) An efficient chemoenzymatic route to dihydroxyacetone phosphate from glycidol for the in situ aldolase-mediated synthesis of monosaccharides. Tetrahedron Lett 47(19):3261–3263

    Article  CAS  Google Scholar 

  45. Bang D, Kent SB (2004) A one-pot total synthesis of crambin. Angew Chem Int Ed Engl 43(19):2534–2538

    Article  CAS  PubMed  Google Scholar 

  46. Schoevaart R, van Rantwijk F, Sheldon RA (2000) A four-step enzymatic cascade for the one-pot synthesis of non-natural carbohydrates from glycerol. J Org Chem 65(21):6940–6943

    Article  CAS  PubMed  Google Scholar 

  47. Gao Q, Wang X, Hu S, Xu N, Jiang M, Ma C et al (2019) High-yield production of D-1,2,4-butanetriol from lignocellulose-derived xylose by using a synthetic enzyme cascade in a cell-free system. J Biotechnol 292:76–83

    Article  CAS  PubMed  Google Scholar 

  48. Schallau K, Junker BH (2010) Simulating plant metabolic pathways with enzyme-kinetic models. Plant Physiol 152(4):1763–1771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Levenspiel O (1999) Chemical reaction engineering, 3rd edn. Wiley, New York

    Google Scholar 

  50. Vasić-Rački Đ, Bongs J, Schorken U, Sprenger GA, Liese A (2003) Modeling of reaction kinetics for reactor selection in the case of L-erythrulose synthesis. Bioprocess Biosyst Eng 25(5):285–290

    Article  PubMed  CAS  Google Scholar 

  51. Dixon M, Webb EC (1979) Enzymes, 3rd edn. Academic Press, New York

    Google Scholar 

  52. Segel IH (1975) Enzyme kinetics: behaviour and analysis of rapid equilibrium and steady state enzyme system. Wiley, New York

    Google Scholar 

  53. Straathof AJJ (2001) Development of a computer program for analysis of enzyme kinetics by progress curve fitting. J Mol Catal B: Enzym 11(4–6):991–998

    Article  CAS  Google Scholar 

  54. France SP, Hepworth LJ, Turner NJ, Flitsch SL (2016) Constructing biocatalytic cascades: in vitro and in vivo approaches to de novo multi-enzyme pathways. ACS Catal 7(1):710–724

    Article  CAS  Google Scholar 

  55. Blackmond DG (2005) Reaction progress kinetic analysis: a powerful methodology for mechanistic studies of complex catalytic reactions. Angew Chem Int Ed Engl 44(28):4302–4320

    Article  CAS  PubMed  Google Scholar 

  56. Scheer M, Grote A, Chang A, Schomburg I, Munaretto C, Rother M et al (2011) BRENDA, the enzyme information system in 2011. Nucleic Acids Res 39(Database issue):D670–D676

    Article  CAS  PubMed  Google Scholar 

  57. Schomburg I, Chang A, Placzek S, Sohngen C, Rother M, Lang M et al (2013) BRENDA in 2013: integrated reactions, kinetic data, enzyme function data, improved disease classification: new options and contents in BRENDA. Nucleic Acids Res 41(Database issue):D764–D772

    CAS  PubMed  Google Scholar 

  58. Krebs O, Golebiewski M, Kania R, Mir S, Saric J, Weidemann A et al (2007) SABIO-RK: a data warehouse for biochemical reactions and their kinetics. J Integr Bioinform 4(1)

    Google Scholar 

  59. Schmidt T, Michalik C, Zavrel M, Spiess A, Marquardt W, Ansorge-Schumacher MB (2010) Mechanistic model for prediction of formate dehydrogenase kinetics under industrially relevant conditions. Biotechnol Prog 26(1):73–78

    CAS  PubMed  Google Scholar 

  60. Bisswanger H (2017) Enzyme kinetics, 3rd edn. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

    Book  Google Scholar 

  61. Chen BH, Hibbert EG, Dalby PA, Woodley JM (2008) A new approach to bioconversion reaction kinetic parameter identification. AIChE J 54(8):2155–2163

    Article  CAS  Google Scholar 

  62. Rios-Solis L, Morris P, Grant C, Odeleye AOO, Hailes HC, Ward JM et al (2015) Modelling and optimisation of the one-pot, multi-enzymatic synthesis of chiral amino-alcohols based on microscale kinetic parameter determination. Chem Eng Sci 122:360–372

    Article  CAS  Google Scholar 

  63. Meissner MP, Nordblad M, Woodley JM (2018) Online measurement of oxygen-dependent enzyme reaction kinetics. Chembiochem 19(1):106–113

    Article  CAS  PubMed  Google Scholar 

  64. Molla GS, Wohlgemuth R, Liese A (2016) One-pot enzymatic reaction sequence for the syntheses of D-glyceraldehyde 3-phosphate and L-glycerol 3-phosphate. J Mol Catal B: Enzym 124:77–82

    Article  CAS  Google Scholar 

  65. Findrik Z, Vasić-Rački Đ (2007) Biotransformation of D-methionine into L-methionine in the cascade of four enzymes. Biotechnol Bioeng 98(5):956–967

    Article  CAS  PubMed  Google Scholar 

  66. Chen BH, Sayar A, Kaulmann U, Dalby PA, Ward JM, Woodley JM (2009) Reaction modelling and simulation to assess the integrated use of transketolase and ω-transaminase for the synthesis of an aminotriol. Biocatal Biotransfor 24(6):449–457

    Article  CAS  Google Scholar 

  67. Al-Haque N, Santacoloma PA, Neto W, Tufvesson P, Gani R, Woodley JM (2012) A robust methodology for kinetic model parameter estimation for biocatalytic reactions. Biotechnol Prog 28(5):1186–1196

    Article  CAS  PubMed  Google Scholar 

  68. Bailey JE, Ollis DF (1986) Biochemical engineering fundamentals, 2nd edn. McGraw-Hill, New York

    Google Scholar 

  69. Sudar M, Findrik Z, Vasić-Rački Đ, Clapés P, Lozano C (2013) Mathematical model for aldol addition catalyzed by two D-fructose-6-phosphate aldolases variants overexpressed in E. coli. J Biotechnol 167(3):191–200

    Article  CAS  PubMed  Google Scholar 

  70. Mitra RK, Woodley JM, Lilly MD (1998) Escherichia coli transketolase-catalyzed carbon-carbon bond formation: biotransformation characterization for reactor evaluation and selection. Enzyme Microb Technol 22(1):64–70

    Article  CAS  Google Scholar 

  71. Mitra RK, Woodley JM, Lilly MD (1999) Process design implications of aldehyde properties on transketolase-catalysed condensations. Biocatal Biotransfor 17(1):21–36

    Article  CAS  Google Scholar 

  72. Bongs J, Hahn D, Schörken U, Sprenger GA, Kragl U, Wandrey C (1997) Continuous production of erythrulose using transketolase in a membrane reactor. Biotechnol Lett 19(3):213–216

    Article  CAS  Google Scholar 

  73. Toscano G, Colarieti ML, Greco G (2003) Oxidative polymerisation of phenols by a phenol oxidase from green olives. Enzyme Microb Technol 33(1):47–54

    Article  CAS  Google Scholar 

  74. Sun X, Yu H, Shen Z (2009) Deactivation kinetics of nitrile hydratase in free resting cells. Chin J Chem Eng 17(5):822–828

    Article  CAS  Google Scholar 

  75. Cantarella M, Cantarella L, Gallifuoco A, Frezzini R, Spera A, Alfani F (2004) A study in UF-membrane reactor on activity and stability of nitrile hydratase from Microbacterium imperiale CBS 498-74 resting cells for propionamide production. J Mol Catal B: Enzym 29(1–6):105–113

    Article  CAS  Google Scholar 

  76. Švarc A, Findrik Blažević Z, Vasić-Rački Đ, Szekrenyi A, Fessner WD, Charnock SJ et al (2019) 2-Deoxyribose-5-phosphate aldolase from Thermotoga maritima in the synthesis of a statin side-chain precursor: characterization, modeling and optimization. J Chem Technol Biotechnol 94:1832–1842

    Google Scholar 

  77. Balcells C, Pastor I, Vilaseca E, Madurga S, Cascante M, Mas F (2014) Macromolecular crowding effect upon in vitro enzyme kinetics: mixed activation-diffusion control of the oxidation of NADH by pyruvate catalyzed by lactate dehydrogenase. J Phys Chem B 118(15):4062–4068

    Article  CAS  PubMed  Google Scholar 

  78. Wheeldon I, Minteer SD, Banta S, Barton SC, Atanassov P, Sigman M (2016) Substrate channelling as an approach to cascade reactions. Nat Chem 8(4):299–309

    Article  CAS  PubMed  Google Scholar 

  79. Zhang YH (2011) Substrate channeling and enzyme complexes for biotechnological applications. Biotechnol Adv 29(6):715–725

    Article  CAS  PubMed  Google Scholar 

  80. Myung S, Zhang YH (2013) Non-complexed four cascade enzyme mixture: simple purification and synergetic co-stabilization. PLoS One 8(4):e61500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zheng Y, Pan Z, Zhang R, Jenkins BM (2009) Kinetic modeling for enzymatic hydrolysis of pretreated creeping wild ryegrass. Biotechnol Bioeng 102(6):1558–1569

    Article  CAS  PubMed  Google Scholar 

  82. Baker P, Hillis C, Carere J, Seah SY (2012) Protein-protein interactions and substrate channeling in orthologous and chimeric aldolase-dehydrogenase complexes. Biochemistry 51(9):1942–1952

    Article  CAS  PubMed  Google Scholar 

  83. Sayar NA, Chen BH, Lye GJ, Woodley JM (2009) Modelling and simulation of a transketolase mediated reaction: sensitivity analysis of kinetic parameters. Biochem Eng J 47(1–3):1–9

    Article  CAS  Google Scholar 

  84. Dvorak P, Kurumbang NP, Bendl J, Brezovsky J, Prokop Z, Damborsky J (2014) Maximizing the efficiency of multienzyme process by stoichiometry optimization. ChemBioChem 15(13):1891–1895

    Article  CAS  PubMed  Google Scholar 

  85. Finnigan W, Cutlan R, Snajdrova R, Adams JP, Littlechild JA, Harmer NJ (2019) Engineering a seven enzyme biotransformation using mathematical modelling and characterized enzyme parts. bioRxiv:603795

    Google Scholar 

  86. Rexer TFT, Schildbach A, Klapproth J, Schierhorn A, Mahour R, Pietzsch M et al (2018) One pot synthesis of GDP-mannose by a multi-enzyme cascade for enzymatic assembly of lipid-linked oligosaccharides. Biotechnol Bioeng 115(1):192–205

    Article  CAS  PubMed  Google Scholar 

  87. Scherkus C, Schmidt S, Bornscheuer UT, Groger H, Kara S, Liese A (2017) Kinetic insights into ε-caprolactone synthesis: improvement of an enzymatic cascade reaction. Biotechnol Bioeng 114(6):1215–1221

    Article  CAS  PubMed  Google Scholar 

  88. Kragl U, Vasić-Rački Đ, Wandrey C (1996) Continuous production of L-tert-leucine in series of two enzyme membrane reactors. Bioprocess Eng 14(6):291–297

    CAS  Google Scholar 

  89. Van Hecke W, Haltrich D, Frahm B, Brod H, Dewulf J, Van Langenhove H et al (2011) A biocatalytic cascade reaction sensitive to the gas–liquid interface: modeling and upscaling in a dynamic membrane aeration reactor. J Mol Catal B: Enzym 68(2):154–161

    Article  CAS  Google Scholar 

  90. Milker S, Fink MJ, Oberleitner N, Ressmann AK, Bornscheuer UT, Mihovilovic MD et al (2017) Kinetic modeling of an enzymatic redox cascade in vivo reveals bottlenecks caused by cofactors. ChemCatChem 9(17):3420–3427

    Article  CAS  Google Scholar 

  91. Wiechert W, Noack S (2011) Mechanistic pathway modeling for industrial biotechnology: challenging but worthwhile. Curr Opin Biotechnol 22(5):604–610

    Article  CAS  PubMed  Google Scholar 

  92. Rollin JA, Martin del Campo J, Myung S, Sun F, You C, Bakovic A et al (2015) High-yield hydrogen production from biomass by in vitro metabolic engineering: mixed sugars coutilization and kinetic modeling. Proc Natl Acad Sci U S A 112(16):4964–4969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kotay SM, Das D (2008) Biohydrogen as a renewable energy resource—prospects and potentials. Int J Hydrogen Energ 33(1):258–263

    Article  CAS  Google Scholar 

  94. Ishii N, Suga Y, Hagiya A, Watanabe H, Mori H, Yoshino M et al (2007) Dynamic simulation of an in vitro multi-enzyme system. FEBS Lett 581(3):413–420

    Article  CAS  PubMed  Google Scholar 

  95. Ardao I, Hwang ET, Zeng AP (2013) In vitro multienzymatic reaction systems for biosynthesis. Adv Biochem Eng Biotechnol 137:153–184

    CAS  PubMed  Google Scholar 

  96. Rosini E, Allegretti C, Melis R, Cerioli L, Conti G, Pollegioni L et al (2016) Cascade enzymatic cleavage of the β-O-4 linkage in a lignin model compound. Catal Sci Technol 6(7):2195–2205

    Article  CAS  Google Scholar 

  97. Mafra AC, Furlan FF, Badino AC, Tardioli PW (2015) Gluconic acid production from sucrose in an airlift reactor using a multi-enzyme system. Bioprocess Biosyst Eng 38(4):671–680

    Article  CAS  PubMed  Google Scholar 

  98. Hoh C, Dudziak G, Liese A (2002) Optimization of the enzymatic synthesis of O-glycan core 2 structure by use of a genetic algorithm. Bioorg Med Chem Lett 12(7):1031–1034

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to acknowledge funding from the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 635595 (CarbaZymes).

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  1. Faculty of Chemical Engineering, University of Zagreb, Zagreb, Croatia

    Martina Sudar & Zvjezdana Findrik Blažević

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  1. Martina Sudar
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Correspondence to Zvjezdana Findrik Blažević .

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  1. Department of Biological and Chemical Engineering, Aarhus University, Aarhus, Denmark

    Selin Kara

  2. Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria

    Florian Rudroff

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Sudar, M., Blažević, Z.F. (2021). Enzyme Cascade Kinetic Modelling. In: Kara, S., Rudroff, F. (eds) Enzyme Cascade Design and Modelling. Springer, Cham. https://doi.org/10.1007/978-3-030-65718-5_6

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