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

Drew V. Carson, Yi Zhang, Larry So, Wai Ling Cheung-Lee, Alexis Jaramillo Cartagena, Seth A. Darst, A. James Link

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2448-2456
Number of pages9
JournalJournal of Natural Products
Volume86
Issue number11
DOIs
StatePublished - Nov 24 2023

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Analytical Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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