Discovery of Ubonodin, an Antimicrobial Lasso Peptide Active against Members of the Burkholderia cepacia Complex

Wai Ling Cheung-Lee; Madison E Parry; Chuhan Zong; Alexis Jaramillo Cartagena; Seth A Darst; Nancy D Connell; Riccardo Russo; A James Link

doi:10.1002/cbic.201900707

Discovery of Ubonodin, an Antimicrobial Lasso Peptide Active against Members of the Burkholderia cepacia Complex

Chembiochem. 2020 May 4;21(9):1335-1340. doi: 10.1002/cbic.201900707. Epub 2020 Jan 3.

Authors

Wai Ling Cheung-Lee¹, Madison E Parry¹, Chuhan Zong², Alexis Jaramillo Cartagena³, Seth A Darst³, Nancy D Connell⁴, Riccardo Russo⁵, A James Link^{1

2

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Affiliations

¹ Department of Chemical and Biological Engineering, Princeton University, 207 Hoyt Laboratory, Princeton, NJ, 08544, USA.
² Department of Chemistry, Princeton University, 207 Hoyt Laboratory, Princeton, NJ, 08544, USA.
³ Laboratory of Molecular Biophysics and, Tri-Institutional Training Program in Chemical Biology, Rockefeller University, 1230 York Ave., New York, NY, 10065, USA.
⁴ Center for Health Security, Johns Hopkins Bloomberg School of Public Health, 621 E. Pratt St. Suite 210, Baltimore, MD, 21202, USA.
⁵ Center for Emerging Pathogens, Division of Infectious Disease, New Jersey Medical School, Rutgers Biomedical and Health Sciences University, 185 South Orange Ave., Newark, NJ, 07103, USA.
⁶ Department of Molecular Biology, Princeton University, 207 Hoyt Laboratory, Princeton, NJ, 08544, USA.

Abstract

We report the heterologous expression, structure, and antimicrobial activity of a lasso peptide, ubonodin, encoded in the genome of Burkholderia ubonensis. The topology of ubonodin is unprecedented amongst lasso peptides, with 18 of its 28 amino acids found in the mechanically bonded loop segment. Ubonodin inhibits RNA polymerase in vitro and has potent antimicrobial activity against several pathogenic members of the Burkholderia genus, most notably B. cepacia and B. multivorans, causative agents of lung infections in cystic fibrosis patients.

Keywords: RiPP; antibiotics; lasso peptides; natural products; peptides.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Burkholderia cepacia complex / classification
Burkholderia cepacia complex / drug effects*
DNA-Directed RNA Polymerases / antagonists & inhibitors*
Drug Discovery*
Humans
Pore Forming Cytotoxic Proteins / chemistry
Pore Forming Cytotoxic Proteins / pharmacology*

Substances

Anti-Bacterial Agents
Pore Forming Cytotoxic Proteins
DNA-Directed RNA Polymerases

Abstract

Publication types

MeSH terms

Substances

Grants and funding