The Rare Amino Acid Building Block 3-(3-furyl)-Alanine in the Formation of Non-ribosomal Peptides

Abstract

Microorganisms have made considerable contributions to the production of peptide secondary metabolites, many of them with therapeutic potential, e.g., the fungus-derived immunosuppressant cyclosporine A and the antibiotic daptomycin originating from Streptomyces. Most of the medically used peptides are the product of non-ribosomal peptide synthetases (NRPS), incorporating apart from proteinogenic also unique, non-proteinogenic amino acids into the peptides. An extremely rare such amino acid is 3-(3-furyl)-alanine. So far, only few peptides have been found that contain this residue, including the rhizonins, bingchamide B and endolides. The producer of the rhizonins was proven to be the bacterial endosymbiont Burkholderia endofungorum inside the fungus Rhizopus microsporus. The microbial origin, chemistry and bioactivity of the 3-(3-furyl)-alanine containing peptides are the focus of this review.