Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides

Amir Pandi (), David Adam, Amir Zare, Trinh Van Tuan, Stefan L. Schaefer, Marie Burt, Björn Klabunde, Elizaveta Bobkova, Manish Kushwaha, Yeganeh Foroughijabbari, Peter Braun, Christoph Spahn, Christian Preußer, Elke Pogge von Strandmann, Helge B. Bode, Heiner Buttlar, Wilhelm Bertrams, Anna Lena Jung, Frank Abendroth, Bernd Schmeck, Gerhard Hummer, Olalla Vázquez and Tobias J. Erb ()
Additional contact information
Amir Pandi: Max Planck Institute for Terrestrial Microbiology
David Adam: Max Planck Institute for Terrestrial Microbiology
Amir Zare: Max Planck Institute for Terrestrial Microbiology
Trinh Van Tuan: Philipps-University Marburg
Stefan L. Schaefer: Max Planck Institute of Biophysics
Marie Burt: Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL)
Björn Klabunde: Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL)
Elizaveta Bobkova: Max Planck Institute for Terrestrial Microbiology
Manish Kushwaha: Micalis Institute
Yeganeh Foroughijabbari: Max Planck Institute for Terrestrial Microbiology
Peter Braun: Bundeswehr Institute of Microbiology
Christoph Spahn: Max Planck Institute for Terrestrial Microbiology
Christian Preußer: Philipps-University Marburg
Elke Pogge von Strandmann: Philipps-University Marburg
Helge B. Bode: Max Planck Institute for Terrestrial Microbiology
Heiner Buttlar: Bundeswehr Institute of Microbiology
Wilhelm Bertrams: Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL)
Anna Lena Jung: Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL)
Frank Abendroth: Philipps-University Marburg
Bernd Schmeck: Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL)
Gerhard Hummer: Max Planck Institute of Biophysics
Olalla Vázquez: Philipps-University Marburg
Tobias J. Erb: Max Planck Institute for Terrestrial Microbiology

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are required to validate candidates in high throughput and at low cost. Here, we established a cell-free protein synthesis (CFPS) pipeline for the rapid and inexpensive production of antimicrobial peptides (AMPs) directly from DNA templates. To validate our platform, we used deep learning to design thousands of AMPs de novo. Using computational methods, we prioritized 500 candidates that we produced and screened with our CFPS pipeline. We identified 30 functional AMPs, which we characterized further through molecular dynamics simulations, antimicrobial activity and toxicity. Notably, six de novo-AMPs feature broad-spectrum activity against multidrug-resistant pathogens and do not develop bacterial resistance. Our work demonstrates the potential of CFPS for high throughput and low-cost production and testing of bioactive peptides within less than 24 h.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42434-9

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DOI: 10.1038/s41467-023-42434-9

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