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Forward design of a complex enzyme cascade reaction.
Christoph Hold1, Sonja Billerbeck1, Sven Panke1
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
Nature Communications
|September 29, 2016
Summary
Researchers designed a 10-enzyme cascade reaction system for fine chemical production. This advancement overcomes complexity challenges in enzymatic reaction networks using engineering systems theory and online mass spectrometry.
Area of Science:
- Biochemistry
- Chemical Engineering
- Systems Biology
Background:
- Enzymatic reaction networks offer one-pot multi-reaction capabilities.
- System complexity and nonlinear enzyme kinetics hinder rational design of cascade reactions.
Purpose of the Study:
- To demonstrate the forward design of a complex, 10-membered in vitro enzymatic system.
- To enable rational optimization of cascade reactions for fine chemical production.
Main Methods:
- Adapted biochemical system characterization to engineering systems theory.
- Combined online mass spectrometry with continuous system operation.
- Applied system theory input functions and analyzed dynamic responses to parameterize a model.
Main Results:
- Successfully designed and parameterized a 10-enzyme cascade reaction system.
- Demonstrated a model suitable for forward design of complex enzymatic networks.
- Facilitated optimization of the cascade for fine chemical synthesis.
Conclusions:
- Forward design of complex enzymatic cascade reactions is achievable.
- Integration of systems engineering principles enhances biochemical system design.
- This approach facilitates efficient fine chemical production using enzymatic networks.
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