Architecture of Microcin B17 Synthetase: An Octameric Protein Complex Converting a Ribosomally Synthesized Peptide into a DNA Gyrase Poison

Mol Cell. 2019 Feb 21;73(4):749-762.e5. doi: 10.1016/j.molcel.2018.11.032. Epub 2019 Jan 17.


The introduction of azole heterocycles into a peptide backbone is the principal step in the biosynthesis of numerous compounds with therapeutic potential. One of them is microcin B17, a bacterial topoisomerase inhibitor whose activity depends on the conversion of selected serine and cysteine residues of the precursor peptide to oxazoles and thiazoles by the McbBCD synthetase complex. Crystal structures of McbBCD reveal an octameric B4C2D2 complex with two bound substrate peptides. Each McbB dimer clamps the N-terminal recognition sequence, while the C-terminal heterocycle of the modified peptide is trapped in the active site of McbC. The McbD and McbC active sites are distant from each other, which necessitates alternate shuttling of the peptide substrate between them, while remaining tethered to the McbB dimer. An atomic-level view of the azole synthetase is a starting point for deeper understanding and control of biosynthesis of a large group of ribosomally synthesized natural products.

Keywords: DNA gyrase; Escherichia coli microcin B17; LAP; RiPP; antibiotic; azole synthetase; cyclodehydratase; dehydrogenase; heterocyclase; protein complex crystal structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacteriocins / biosynthesis*
  • Bacteriocins / chemistry
  • Bacteriocins / pharmacology
  • Binding Sites
  • Crystallography, X-Ray
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Models, Molecular
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Mutation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Ribosomes / drug effects
  • Ribosomes / enzymology*
  • Ribosomes / genetics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / metabolism*
  • Topoisomerase II Inhibitors / pharmacology
  • X-Ray Diffraction


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacteriocins
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • Topoisomerase II Inhibitors
  • microcin B17 synthase
  • microcin