Year: 2026
Type: article
Abstract: Protein allostery underlies most information and energy processing in biology and the development of artificial allosteric proteins is a key objective of synthetic biology and biotechnology. We show that machine-learning-engineered minimal ligand-binding domains act as efficient receptors in single-component allosteric switches, despite lacking global conformational change. Such colorimetric, luminescent and electrochemical biosensors of small molecules, peptides and proteins can be compiled into intramolecular YES and AND logic gates. Furthermore, we report fully synthetic allosteric switches composed of artificial receptor and reporter domains. Hydrogen/deuterium exchange mass spectrometry and 19 F nuclear magnetic resonance analyses suggest that ligand binding reduces the conformation entropy of the system, increasing the catalytic activity of the reporter domain. The potential practical utility of this approach is demonstrated by engineering Escherichia coli cells with steroid-dependent antibiotic resistance and by developing bioelectronic devices capable of quantifying steroid hormones.
Source: Nature Biotechnology
Authors: Zhong Guo, Oleh Smutok, Gyu Rie Lee, Zhenling Cui, Haocheng Qianzhu, Monika Kish, Cagla Ergun Ayva, Kejia Wu, Roxane Mutschler, Colin J. Jackson, Maria M. Fiorito, Andrew C. Warden, Oliver B. Smith, Alfredo Quijano-Rubio, Thomas Huber, Jonathan J. Phillips, Gottfried Otting, Evgeny Katz, David Baker, Kirill Alexandrov
Institutions: Queensland University of Technology, ARC Centre of Excellence in Synthetic Biology, Clarkson University, Howard Hughes Medical Institute, Korea Advanced Institute of Science and Technology, University of Washington, Commonwealth Scientific and Industrial Research Organisation, Australian National University, University of Exeter, ARC Centre of Excellence for Innovations in Peptide and Protein Science, CSIRO Environment
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: National Science Foundation, Howard Hughes Medical Institute, Open Philanthropy Project, Commonwealth Scientific and Industrial Research Organisation, Medical Research Council, Australian Research Council, National Health and Medical Research Council, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: Engineering electrochemical protein biosensors, Protein Structure and Dynamics by Electron/Nuclear Paramagnetic Resonance, NSF-BSF: Development of a Chimera Enzyme Switch for Branched-chain Amino Acids Biosensing, Protein Choreography, G2899358719, Protein biosensors for detecting smoke exposure of grapes, G5214386507, Artificial protein circuits and the next generation diagnostics, G5572172683, G6182535003, A Universal Biosensing Platform Amplifying Signals Produced by NAD+/NADH-Dependent Enzymes, Non-Canonical Amino Acids for Protein Analysis and Peptide Inhibitors, G6505962787, G6727372865, G8774149294, ARC Centre of Excellence in Synthetic Biology
OpenAlex ID: W7154482158