The discovery, isolation, structure elucidation and total synthesis of the fuscachelins, nonribosomal peptide siderophores form the thermophilic actinomycete Thermobifida fusca

The fuscachelins are a group of novel small molecule secondary metabolites produced by the thermophilic actinomycete Thermobifida fusca. A genome mining approach was employed to identify the fuscachelin nonribosomal peptide synthetase biosynthetic gene cluster in T. fusca . The peptide natural products were predicted to be siderophores, iron-scavenging small molecules. An assay guided fractionation approach was utilized to isolate the fuscachelins. Structure elucidation efforts employed nuclear magnetic resonance, mass spectrometric and chemical degradation techniques to determine the structure of the isolated compounds. Once the structure was known, a total synthesis was undertaken. The established synthetic route to the fuscachelins will allow for the facile development of custom-designed chemical tools for the further study of the fuscachelin biosynthetic enzymes and utilization proteins.