Mimicking Nonribosomal Peptides from the Marine Actinomycete Streptomyces sp. H-KF8 Leads to Antimicrobial Peptides
Journal article, 2024
Microorganisms within the marine environment have been shown to be very effective sources of naturally produced antimicrobial peptides (AMPs). Several nonribosomal peptides were identified based on genome mining predictions of Streptomyces sp. H-KF8, a marine Actinomycetota isolated from a remote Northern Chilean Patagonian fjord. Based on these predictions, a series of eight peptides, including cyclic peptides, were designed and chemically synthesized. Six of these peptides showed antimicrobial activity. Mode of action studies suggest that two of these peptides potentially act on the cell membrane via a novel mechanism allowing the passage of small ions, resulting in the dissipation of the membrane potential. This study shows that though structurally similar peptides, determined by NMR spectroscopy, the incorporation of small sequence mutations results in a dramatic influence on their bioactivity including mode of action. The qualified hit sequence can serve as a basis for more potent AMPs in future studies.
cyclic peptides
marine sediments
antimicrobial peptides
nonribosomal peptides
secondary metabolite
Streptomyces
Author
Luisa I. Beyer
University of Gothenburg
Ann-Britt Schäfer
Chalmers, Life Sciences, Chemical Biology
University of Gothenburg
Agustina Undabarrena
Universidad Técnica Federico Santa María
Inger Mattsby-Baltzer
University of Gothenburg
Daniel Tietze
University of Gothenburg
Elin Svensson
Chalmers, Life Sciences, Chemical Biology
Alexandra Stubelius
Chalmers, Life Sciences, Chemical Biology
Michaela Wenzel
University of Gothenburg
Chalmers, Life Sciences, Chemical Biology
Beatriz Cámara
Universidad Técnica Federico Santa María
Alesia A. Tietze
University of Gothenburg
ACS Infectious Diseases
2373-8227 (eISSN)
Vol. 10 1 79-92Gender Initiative for Excellence (Genie)
The Chalmers University Foundation, 2019-01-01 -- 2028-12-31.
Interaction of antibiotics with bacterial cells
Chalmers, 2019-09-02 -- 2023-08-31.
Chalmers, 2024-01-01 -- 2026-12-31.
Subject Categories (SSIF 2025)
Molecular Biology
Cell and Molecular Biology
Bioinformatics (Computational Biology)
Bioinformatics and Computational Biology
Cell Biology
Microbiology in the Medical Area
Microbiology
Pharmaceutical Sciences
Oceanography, Hydrology and Water Resources
Pharmacology and Toxicology
Organic Chemistry
Medicinal Chemistry
Biochemistry
Medical Bioinformatics and Systems Biology
Roots
Basic sciences
Areas of Advance
Health Engineering
Subject Categories (SSIF 2011)
Microbiology
DOI
10.1021/acsinfecdis.3c00206
PubMed
38113038