Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis

Cell Chem Biol. 2016 Mar 17;23(3):370-380. doi: 10.1016/j.chembiol.2015.11.017. Epub 2016 Feb 11.


Class I lantibiotic dehydratases dehydrate selected Ser/Thr residues of a precursor peptide. Recent studies demonstrated the requirement of glutamyl-tRNA(Glu) for Ser/Thr activation by one of these enzymes (NisB) from the Firmicute Lactococcus lactis. However, the generality of glutamyl-tRNA(Glu) usage and the tRNA specificity of lantibiotic dehydratases have not been established. Here we report the 2.7-Å resolution crystal structure, along with the glutamyl-tRNA(Glu) utilization of MibB, a lantibiotic dehydratase from the Actinobacterium Microbispora sp. 107891 involved in the biosynthesis of the clinical candidate NAI-107. Biochemical assays revealed nucleotides A73 and U72 within the tRNA(Glu) acceptor stem to be important for MibB glutamyl-tRNA(Glu) usage. Using this knowledge, an expression system for the production of NAI-107 analogs in Escherichia coli was developed, overcoming the inability of MibB to utilize E. coli tRNA(Glu). Our work provides evidence for a common tRNA(Glu)-dependent dehydration mechanism, paving the way for the characterization of lantibiotics from various phyla.

Publication types

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

MeSH terms

  • Actinobacteria / cytology
  • Actinobacteria / enzymology*
  • Bacteriocins / biosynthesis
  • Bacteriocins / chemistry
  • Bacteriocins / metabolism*
  • Hydro-Lyases / chemistry*
  • Hydro-Lyases / metabolism*
  • Models, Molecular
  • Molecular Conformation
  • RNA, Transfer / chemistry*
  • RNA, Transfer / metabolism*
  • Substrate Specificity


  • Bacteriocins
  • microbisporicin
  • RNA, Transfer
  • Hydro-Lyases