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Publications

Journal Article Ahead of print 5 citations

PubMed: 41520285 DOI: 10.1021/acssensors.5c02481

A Novel Biosensor for Ferrous Iron Developed via CoBiSe: A Computational Method for Rapid Biosensor Design.

ACS Sens

Authors: Athanasios Papadopoulos, Manuel T Anlauf, Jens Reiners, Seung-Hyun Paik, Aileen Krüger, Benita Lückel, Michael Bott, Thomas Drepper, Julia Frunzke, Holger Gohlke, Stefanie Weidtkamp-Peters, Sander H J Smits, Christoph G W Gertzen

Affiliations

  • Center for Structural Studies, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
  • Center for Advanced Imaging, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
  • Institute of Molecular Enzyme Technology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Institute of Microbial Interactions, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
  • Institute of Bio- and Geosciences (IBG-1: Biotechnology), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Institute of Bio- and Geosciences (IBG-4: Bioinformatics), Forschungszentrum Jülich, 52428 Jülich, Germany.
  • Institute for Pharmaceutical and Medicinal Chemistry, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
  • Institute for Biochemistry, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.

Abstract

Genetically encoded biosensors enable the monitoring of metabolite dynamics in living organisms. We present CoBiSe, a computational biosensor design approach using Constraint Network Analysis to identify optimal insertion sites for reporter modules in molecular recognition elements (MREs). Applied to the iron-binding protein DtxR from Corynebacterium glutamicum, CoBiSe identified a flexible connective loop (residues 138-150) for inserting the reporter module, resulting in IronSenseR, a novel ratiometric biosensor for ferrous iron (Fe 2+). IronSenseR demonstrates high specificity for Fe 2+ with dissociation constants of 1.78 ± 0.03 (FeSO 4) and 2.90 ± 0.12 μM (FeCl 2), while showing no binding to Fe 3+ and other divalent cations. In vivo assessment in Escherichia coli, Pseudomonas putida, and Corynebacterium glutamicum confirmed IronSenseR's capability to detect changes in the intracellular iron pool. The creation of IronSenseR underlines that by reducing search space and eliminating labor-intensive screening, CoBiSe streamlines biosensor development and enables precise creation of next-generation biosensors for diverse metabolites.

MeSH

Bacteria