The pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide

Fernando Baquero; Konstantinos Beis; David J. Craik; Yanyan Li; A. James Link; Sylvie Rebuffat; Raúl Salomón; Konstantin Severinov; Séverine Zirah; Julian D. Hegemann

doi:10.1039/D3NP00046J

The pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide

Fernando Baquero,

^ab Konstantinos Beis,

^cd David J. Craik,

^e Yanyan Li,

^f A. James Link,

^g Sylvie Rebuffat,

^f Raúl Salomón,^h Konstantin Severinov,ⁱ Séverine Zirah

^f and Julian D. Hegemann

*^jk

Author affiliations

* Corresponding authors

^a Department of Microbiology, Ramón y Cajal University Hospital and Ramón y Cajal Institute for Health Research (IRYCIS), Madrid, Spain

^b Network Center for Research in Epidemiology and Public Health (CIBER-ESP), Madrid, Spain

^c Department of Life Sciences, Imperial College London, London, UK

^d Rutherford Appleton Laboratory, Research Complex at Harwell, Didcot, Oxfordshire OX11 0FA, UK

^e Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, 4072 Brisbane, Queensland, Australia

^f Laboratoire Molécules de Communication et Adaptation des Microorganismes (MCAM), UMR 7245, Muséum National d'Histoire Naturelle (MNHN), Centre National de la Recherche Scientifique (CNRS), Paris, France

^g Departments of Chemical and Biological Engineering, Chemistry, and Molecular Biology, Princeton University, Princeton, NJ 08544, USA

^h Instituto de Química Biológica “Dr Bernabé Bloj”, Facultad de Bioquímica, Química y Farmacia, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, San Miguel de Tucumán, Argentina

ⁱ Waksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

^j Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University Campus, 66123 Saarbrücken, Germany
E-mail: julian.hegemann@helmholtz-hips.de

^k Department of Pharmacy, Campus E8 1, Saarland University, 66123 Saarbrücken, Germany

Abstract

Covering: 1992 up to 2023

Since their discovery, lasso peptides went from peculiarities to be recognized as a major family of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products that were shown to be spread throughout the bacterial kingdom. Microcin J25 was first described in 1992, making it one of the earliest known lasso peptides. No other lasso peptide has since then been studied to such an extent as microcin J25, yet, previous review articles merely skimmed over all the research done on this exceptional lasso peptide. Therefore, to commemorate the 30th anniversary of its first report, we give a comprehensive overview of all literature related to microcin J25. This review article spans the early work towards the discovery of microcin J25, its biosynthetic gene cluster, and the elucidation of its three-dimensional, threaded lasso structure. Furthermore, the current knowledge about the biosynthesis of microcin J25 and lasso peptides in general is summarized and a detailed overview is given on the biological activities associated with microcin J25, including means of self-immunity, uptake into target bacteria, inhibition of the Gram-negative RNA polymerase, and the effects of microcin J25 on mitochondria. The in vitro and in vivo models used to study the potential utility of microcin J25 in a (veterinary) medicine context are discussed and the efforts that went into employing the microcin J25 scaffold in bioengineering contexts are summed up.

Graphical abstract: The pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide

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The pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide

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