A genome-wide approach for identification and characterisation of metabolite-inducible systems

Hanko, Erik K R; Paiva, Ana C; Jonczyk, Magdalena; Abbott, Matthew; Minton, Nigel P.; Malys, Naglis

Abstract

© 2020, The Author(s). Inducible gene expression systems are vital tools for the advancement of synthetic biology. Their application as genetically encoded biosensors has the potential to contribute to diagnostics and to revolutionise the field of microbial cell factory development. Currently, the number of compounds of biological interest by far exceeds the number of available biosensors. Here, we address this limitation by developing a generic genome-wide approach to identify transcription factor-based inducible gene expression systems. We construct and validate 15 functional biosensors, provide a characterisation workflow to facilitate forward engineering efforts, exemplify their broad-host-range applicability, and demonstrate their utility in enzyme screening. Previously uncharacterised interactions between sensors and compounds of biological relevance are identified by employing the largest reported library of metabolite-responsive biosensors in an automated high-throughput screen. With the rapidly growing genomic data these innovative capabilities offer a platform to vastly increase the number of biologically detectable molecules.

Citation

Hanko, E. K. R., Paiva, A. C., Jonczyk, M., Abbott, M., Minton, N. P., & Malys, N. (2020). A genome-wide approach for identification and characterisation of metabolite-inducible systems. Nature Communications, 11(1), https://doi.org/10.1038/s41467-020-14941-6

• Journal Article Type: Article
• Acceptance Date: Feb 7, 2020
• Online Publication Date: Mar 5, 2020
• Publication Date: Mar 5, 2020
• Deposit Date: Feb 13, 2020
• Publicly Available Date: Mar 5, 2020
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 1
• Article Number: 1213
• DOI: https://doi.org/10.1038/s41467-020-14941-6
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/3958514
• Publisher URL: https://www.nature.com/articles/s41467-020-14941-6
• Additional Information: Received: 19 September 2019; Accepted: 7 February 2020; First Online: 5 March 2020; : The authors declare no competing interests.