Structural basis of nonribosomal peptide macrocyclization in fungi

Nat Chem Biol. 2016 Dec;12(12):1001-1003. doi: 10.1038/nchembio.2202. Epub 2016 Oct 17.

Abstract

Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (CT) domain and the holo thiolation (T)-CT complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.

MeSH terms

  • Biological Products / chemistry
  • Biological Products / metabolism
  • Crystallography, X-Ray
  • Cyclization
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / metabolism
  • Models, Molecular
  • Molecular Structure
  • Penicillium / enzymology*
  • Peptide Synthases / chemistry*
  • Peptide Synthases / metabolism*
  • Peptides / chemistry*
  • Peptides / metabolism*

Substances

  • Biological Products
  • Macromolecular Substances
  • Peptides
  • Peptide Synthases
  • non-ribosomal peptide synthase