| Autor: |
Carson DV; Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States., Zhang Y; Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States., So L; Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States., Cheung-Lee WL; Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States., Cartagena AJ; Laboratory of Molecular Biophysics and Tri-Institutional Training Program in Chemical Biology, Rockefeller University, New York, New York 10065, United States., Darst SA; Laboratory of Molecular Biophysics and Tri-Institutional Training Program in Chemical Biology, Rockefeller University, New York, New York 10065, United States., Link AJ; Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.; Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, United States.; Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States. |
| Abstrakt: |
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. |
