Peptaibiomics: towards a myriad of bioactive peptides containing C(alpha)-dialkylamino acids?

Fungi are generally regarded as a literally infinite resource of bioactive secondary metabolites displaying remarkable structural diversity. Research on a particular group of linear and cyclic peptide antibiotics comprehensively named peptaibiotics--as result of the abundance of the non-proteinogenic C(alpha)-dialkylated alpha-amino acids alpha-aminoisobutyric acid (Aib) and isovaline (Iva)--has been started 50 years ago. These peptides have gained constantly increasing interest because of their unique bioactivities and conformations. This review, reflecting the history of peptaibiotic research from 1958 to 2008, is focussed on introducing both the structural diversity and natural microheterogeneity of the peptaibiotics, as well as the biodiversity of their fungal producers. Recently introduced state-of-the-art methods for rapid screening and sequencing of peptaibiotics, such as peptaibiomics and intact-cell MALDI-TOF mass spectrometry, are discussed. Finally, future prospects in peptaibiotic research are presented. Owing to the ubiquity and biodiversity of the fungal producers in the biosphere, the discovery of a myriad of peptaibiotics within the next decade is predicted.