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.
antimicrobial peptides
secondary metabolite
marine sediments
Streptomyces
cyclic peptides
nonribosomal peptides
Author
Luisa I. Beyer
University of Gothenburg
Ann-Britt Schäfer
University of Gothenburg
Chalmers, Life Sciences, Chemical Biology
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
Chalmers, Life Sciences, Chemical Biology
University of Gothenburg
Beatriz Cámara
Universidad Técnica Federico Santa María
Alesia A. Tietze
University of Gothenburg
ACS Infectious Diseases
2373-8227 (eISSN)
Vol. 10 1 79-92Subject Categories
Microbiology
DOI
10.1021/acsinfecdis.3c00206
PubMed
38113038