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Forward design of a complex enzyme cascade reaction

Author

Listed:
  • Christoph Hold

    (Department of Biosystems Science and Engineering)

  • Sonja Billerbeck

    (Department of Biosystems Science and Engineering
    Present address: Department of Systems Biology, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA)

  • Sven Panke

    (Department of Biosystems Science and Engineering)

Abstract

Enzymatic reaction networks are unique in that one can operate a large number of reactions under the same set of conditions concomitantly in one pot, but the nonlinear kinetics of the enzymes and the resulting system complexity have so far defeated rational design processes for the construction of such complex cascade reactions. Here we demonstrate the forward design of an in vitro 10-membered system using enzymes from highly regulated biological processes such as glycolysis. For this, we adapt the characterization of the biochemical system to the needs of classical engineering systems theory: we combine online mass spectrometry and continuous system operation to apply standard system theory input functions and to use the detailed dynamic system responses to parameterize a model of sufficient quality for forward design. This allows the facile optimization of a 10-enzyme cascade reaction for fine chemical production purposes.

Suggested Citation

  • Christoph Hold & Sonja Billerbeck & Sven Panke, 2016. "Forward design of a complex enzyme cascade reaction," Nature Communications, Nature, vol. 7(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12971
    DOI: 10.1038/ncomms12971
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    Cited by:

    1. Bob Sluijs & Tao Zhou & Britta Helwig & Mathieu G. Baltussen & Frank H. T. Nelissen & Hans A. Heus & Wilhelm T. S. Huck, 2024. "Iterative design of training data to control intricate enzymatic reaction networks," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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