Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition

Dmitrii Y. Travin, Zoe L. Watson, Mikhail Metelev, Fred R. Ward, Ilya A. Osterman, Irina M. Khven, Nelli F. Khabibullina, Marina Serebryakova, Peter Mergaert, Yury S. Polikanov, Jamie H.D. Cate, Konstantin Severinov

    Research output: Contribution to journalArticlepeer-review

    21 Citations (Scopus)

    Abstract

    Ribosome-synthesized post-translationally modified peptides (RiPPs) represent a rapidly expanding class of natural products with various biological activities. Linear azol(in)e-containing peptides (LAPs) comprise a subclass of RiPPs that display outstanding diversity of mechanisms of action while sharing common structural features. Here, we report the discovery of a new LAP biosynthetic gene cluster in the genome of Rhizobium Pop5, which encodes the precursor peptide and modification machinery of phazolicin (PHZ) – an extensively modified peptide exhibiting narrow-spectrum antibacterial activity against some symbiotic bacteria of leguminous plants. The cryo-EM structure of the Escherichia coli 70S-PHZ complex reveals that the drug interacts with the 23S rRNA and uL4/uL22 proteins and obstructs ribosomal exit tunnel in a way that is distinct from other compounds. We show that the uL4 loop sequence determines the species-specificity of antibiotic action. PHZ expands the known diversity of LAPs and may be used in the future as biocontrol agent for agricultural needs.

    Original languageEnglish
    Article number4563
    JournalNature Communications
    Volume10
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2019

    Fingerprint

    Dive into the research topics of 'Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition'. Together they form a unique fingerprint.

    Cite this