ERC-CoG project – RECYPION

The ERC Consolidator project RECYPION aims to investigate a class of complex natural products, collectively referred to as carboxyl polyether ionophores (CPIs), as antibiotics to target resistant bacterial infections. The antimicrobial resistance (AMR) crisis, that humanity has unfortunately only just started to experience, will be one of the largest healthcare challenges in the 21st century. There is no doubt that antibiotics with mechanisms that are not readily subject to resistance development will be needed and the CPIs fit this profile to the point. The CPIs have been known for >50 years, but despite numerous studies in the past, its remains unclear exactly how the different members of this class exert their antibiotic potency. RECYPION e.g. aims to leverage the methods of organic chemistry and advanced analytics to both widen the therapeutic window of the CPI-antibiotics but also gain new insights into the cellular mechanisms of these compounds.

Find press releases about the project from Nature Chemistry, Aarhus University, Dagens Medicin (Danish) and Carlsbergfondet (Danish) by following the links.

Preprints

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F. E. H. Kromm*, S. L. B. Møller*, G. J. Wørmer, A. S. Jensen, M. H. Rasmussen, E. B. Svenningsen, T. Tørring, T. B. Poulsen, “Modular total synthesis of Lasalocid acid A through direct C(sp3)-C(sp3) attached ring coupling”, ChemRxiv, 2025, DOI: 10.26434/chemrxiv-2025-4r44q

*These authors contributed equally

Find the new paper from Esben, Florian and collaborators from the Department of Biomedicine describing detection of the oxidation state of N-terminal cysteines in XXX now.

E. B. Svenningsen, F. Demir, F. E. H. Kromm, A. H. F. Rahimic, D. Olagnier, M. M. Rinschen, T. B. Poulsen, “Chemoproteomic mapping of the N-terminal cysteinome”, ChemRxiv, 2024, DOI: 10.26434/chemrxiv-2024-4w549

Peer-reviewed publications

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72. M. H. Rasmussen, S. L. B. Møller, E. B. Svenningsen, T. Tørring, T. B. Poulsen, “P450 Enzyme LyoI Performs Hydro-2,2′-Bifuran Oxidation in the Polyether Ionophore Lysocellin”, Angew. Chem. Int. Ed., 2025, e202507847, DOI: 10.1002/anie.202507847

First seen on ChemRxiv: doi.org/10.26434/chemrxiv-2025-bdxkm

70. M. D. Opfermann, M. B. Søndergård, L. V. Bech, C. B. Nielsen, A. Mahía, C. B. Holt , T. Wang, S. B. Olesen, K. Frisch, J. A. Østergaard, D. Britz, K. L. Nielsen, J. J. Galligan, T. B. Poulsen, J. Hansen, M. Johannsen, “Reactivity-based metabolomics reveal cysteine has glyoxalase 1-like and glyoxalase 2-like activities”, Nat. Chem. Biol., 2025, 21, 1397-1407, DOI: 10.1038/s41589-025-01909-0

Thomas and Anders' work on cyclohelminthol II as a new cysteine-selective covalent reactive group has been published in Chemical Science!

69. T. T. Paulsen*, A. E. Kiib*, G. J. Wørmer, S. M. Hacker, T. B. Poulsen, “Total syntheses of cyclohelminthol I–IV reveal a new cysteine-selective covalent reactive group”, Chem. Sci., 2025, 16, 3916-3927, DOI: 10.1039/d4sc08667h

*These authors contributed equally

Check out ChemBioChem for the newest findings about the biological activity of Routiennocin made possible by Søren's synthesis of its enantiomer.

64. S. L. B. Møller, M. H. Rasmussen, J. Li, E. B. Svenningsen, G. J. Wørmer, T. Tørring, T. B. Poulsen, “The Biological Activities of Polyether Ionophore Antibiotic Routiennocin is Independent of Absolute Stereochemistry”, ChemBioChem, 2024, 25, e202400013, DOI: 10.1002/cbic.202400013

61. M. Wollesen, K. Mikkelsen, M. S. Tvilum, M. Vestergaard, M. Wang, R. L. Meyer, H. Ingmer, T. B. Poulsen, T. Tørring, “Polyether Ionophore Antibiotics Target Drug-Resistant Clinical Isolates, Persister Cells, and Biofilms”, Microbiol. Spectr., 2023, 11, e00625-23, DOI: 10.1128/spectrum.00625-23

First seen on BioRxiv:doi.org/10.1101/2023.02.13.528344

59. A. Mahía, A. E. Kiib, M. Nisavic, E. B. Svenningsen, J. Palmfeldt, T. B. Poulsen, “α-Lactam Electrophiles for Covalent Chemical Biology”, Angew. Chem. Int. Ed., 2023, 62, e202304142, DOI: 10.1002/anie.202304142

First seen on ChemRxiv: doi.org/10.26434/chemrxiv-2022-p4wtd

Read Thomas' contribution to the special issue of Acc. Chem. Res. on Total Synthesis of Natural Products

50. T. B. Poulsen, "Total Synthesis of Natural Products Containing Enamine or Enol Ether Derivatives", Acc. Chem. Res., 2021, 54, 1830–1842, DOI: 10.1021/acs.accounts.0c00851
Contribution to Acc. Chem. Res. special issue on “Total Synthesis of Natural Products”

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Our work on expanding the capabilities of the polyether ionophores has been published in Nature Chemistry

48. S. Lin, H. Liu, E. B. Svenningsen, M. Wollesen, K. M. Jacobsen, F. D. Andersen, J. Moyano-Villameriel, C. N. Pedersen, P. Nørby, T. Tørring, T. B. Poulsen, "Expanding the Antibacterial Selectivity of Polyether Ionophore Antibiotics through Diversity-Focused Semisynthesis", Nat. Chem., 2021, 13, 47–55, DOI: 10.1038/s41557-020-00601-1

First seen on ChemRxiv: doi.org/10.26434/chemrxiv.8299715.v1

Read our paper on the discovery of the polyether ionophore X-206 as a potent inhibitor of SARS-CoV-2 infection in vitro

47. E. B. Svenningsen, J. Thyrsted, J. Blay-Cadanet, H. Liu, S. Lin, J. Moyano-Villameriel, D. Olagnier, M. Idorn, S. R. Paludan, C. K. Holm, T. B. Poulsen, "Ionophore Antibiotic X-206 Is a Potent Inhibitor of SARS-CoV-2 Infection in Vitro", Antiviral Res., 2021, 185, 104988, DOI: 10.1016/j.antiviral.2020.104988

First seen on BioRxiv: doi.org/10.1101/2020.06.14.149153