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

Through genome mining efforts, we discovered two lasso peptide biosynthetic gene clusters (BGCs) within two different species of , a genus that contains pathogenic organisms that can infect patients with cystic fibrosis. Using gene-refactored BGCs in , we heterologously expressed two lasso peptides, which we named achromonodin-1 and achromonodin-2. Achromonodin-1 is naturally encoded by certain isolates from the sputum of patients with cystic fibrosis. We solve the NMR structure of achromonodin-1, 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). We then show that achromonodin-1 inhibits RNAP and has potent but narrow-spectrum activity towards , another isolate from the sputum of a cystic fibrosis patient. Our efforts expand the repertoire of antimicrobial lasso peptides and provide insights into how isolates from certain ecological niches may interact with each other.

Duke Scholars

Author Alexis Jaramillo Cartagena Pathology