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A nanoengineered tandem nitroreductase: designing a robust prodrug-activating nanoreactor
Mariia Zmyslia1, Michael J Capper2, Michael Grimmeisen1
1Institute of Organic Chemistry, University of Freiburg 79104 Freiburg im Breisgau Germany claudia.jessen-trefzer@pharmazie.uni-freiburg.de.
RSC Chemical Biology
|November 7, 2024
Summary
Encapsulating nitroreductase enzymes within protein shells called encapsulins boosts their stability and activity. Specific mutations enhance enzyme function, showing potential for improved applications in medicine and environmental cleanup.
Area of Science:
- Biochemistry and Molecular Biology
- Biotechnology
- Enzyme Engineering
Background:
- Nitroreductases are crucial enzymes with applications in cancer therapy and bioremediation.
- Enzyme stability and activity are often enhanced through encapsulation.
- Protein capsids, such as encapsulins, offer a platform for genetically encoded enzyme encapsulation.
Purpose of the Study:
- To investigate the genetically encoded encapsulation of nitroreductase NfsB within encapsulins.
- To evaluate the impact of encapsulation on NfsB activity and stability.
- To explore the structural basis for enhanced enzyme performance within the encapsulin nanoreactor.
Main Methods:
- Genetically encoded expression of nitroreductase NfsB within encapsulins.
- Biochemical assays to measure enzyme activity and stability under various conditions.
- Cryogenic electron microscopy (cryo-EM) for structural analysis of encapsulated NfsB.
Main Results:
- Successful encapsulation of functional dimeric NfsB within encapsulins.
- Demonstrated enhancement of NfsB activity and stability upon encapsulation.
- Identification of beneficial mutations in the encapsulin pore region, potentially improving substrate diffusion.
- Cryo-EM revealed the architecture of encapsulated dimeric NfsB and multiple states of the encapsulin shell pores.
Conclusions:
- Encapsulins serve as effective nanoreactors for enhancing nitroreductase enzyme performance.
- Genetic encapsulation offers a versatile strategy for improving enzyme stability and activity for diverse applications.
- Structural insights into pore states provide a basis for further engineering of encapsulin-based biocatalysts.
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