Discovery, Characterization, and Bioactivity of the Achromonodins: Lasso Peptides Encoded by Achromobacter.

Abstract

Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of Achromobacter, a genus that contains pathogenic organisms that can infect patients with cystic fibrosis, were discovered. Using gene-refactored BGCs in E. coli, these lasso peptides, which were named achromonodin-1 and achromonodin-2, were heterologously expressed. Achromonodin-1 is naturally encoded by certain isolates from the sputum of patients with cystic fibrosis. The NMR structure of achromonodin-1 was determined, demonstrating that it is a threaded lasso peptide with a large loop and short tail structure, reminiscent of previously characterized lasso peptides that inhibit RNA polymerase (RNAP). Achromonodin-1 inhibits RNAP in vitro and has potent, focused activity toward Achromobacter pulmonis, another isolate from the sputum of a cystic fibrosis patient. These efforts expand the repertoire of antimicrobial lasso peptides and provide insights into how Achromobacter isolates from certain ecological niches interact with each other.

• Authors: Drew V Carson, Yi Zhang, Larry So, Wai Ling Cheung-Lee, Alexis Jaramillo Cartagena, Seth A Darst, A James Link
• Journal: Journal of natural products (J Nat Prod) Vol. 86 Issue 11 Pg. 2448-2456 (11 24 2023) ISSN: 1520-6025 [Electronic] United States
• PMID: 37870195 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• Antimicrobial Peptides
• DNA-Directed RNA Polymerases

Topics

• Humans
• Escherichia coli
• Cystic Fibrosis
• Peptides (chemistry)
• Antimicrobial Peptides
• Achromobacter
• DNA-Directed RNA Polymerases