A nanoengineered tandem nitroreductase

designing a robust prodrug-activating nanoreactor

authored by

Mariia Zmyslia, Michael J. Capper, Michael Grimmeisen, Kerstin Sartory, Benedikt Deuringer, Mohamed Abdelsalam, Kaiwei Shen, Manfred Jung, Wolfgang Sippl, Hans Georg Koch, Laurine Kaul, Regine Süss, Jesko Köhnke, Claudia Jessen-Trefzer

Abstract

Nitroreductases are important enzymes for a variety of applications, including cancer therapy and bioremediation. They often require encapsulation to improve stability and activity. We focus on genetically encoded encapsulation of nitroreductases within protein capsids, like encapsulins. Our study showcases the encapsulation of nitroreductase NfsB as functional dimers within encapsulins, which enhances protein activity and stability in diverse conditions. Mutations within the pore region are beneficial for activity of the encapsulated enzyme, potentially by increasing diffusion rates. Cryogenic electron microscopy reveals the overall architecture of the encapsulated dimeric NfsB within the nanoreactor environment and identifies multiple pore states in the shell. These findings highlight the potential of encapsulins as versatile tools for enhancing enzyme performance across various fields.

Organisation(s)

Institute of Food Chemistry

External Organisation(s)

University of Freiburg
University of Glasgow
Martin Luther University Halle-Wittenberg
Alexandria University

Type

Article

Journal

RSC Chemical Biology

Publication date

04.11.2024

Publication status

E-pub ahead of print

Peer reviewed

Yes

ASJC Scopus subject areas

Chemistry (miscellaneous), Biochemistry, Molecular Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous)

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1039/d4cb00127c (Access: Open)