1.D.83. The Pore-forming Lipopeptide Iturin (Iturin) Family
Iturins are membeers of a family of lipopeptides extracted from the culture media of various strains of Bacillus subtilis. These amphiphilic compounds are characterized by a peptide ring of seven amino acid residues including an invariable D-Tyr2, with the constant chiral sequence LDDLLDL closed by a C14-C17 aliphatic β-amino acid. They exhibit strong antifungal activities against a wide variety of pathogenic yeasts and fungi, but their antibacterial activities are restricted to some bacteria such as Micrococcus luteus (Maget-Dana and Peypoux 1994). The biological activities of the iturin lipopeptides are modulated by the primary structure of the peptide cycle as illustrated by the methylation of the D-Tyr2 residue which dramatically decreases the activities, or by the inversion of the two adjacent Ser6-Asn7 residues, which makes mycosubtilin more active than iturin A. The antifungal activity is related to the interaction of the iturin lipopeptides with the cytoplasmic membrane of target cells, the K+ permeability of which is greatly increased. The ability of iturins to increase the cell membrane permeability is due to the formation of ion-conducting pores, the characteristics of which depend both on the lipid composition of the membrane and on the structure of the peptide cycle. From monolayer experiments, it has been suggested that these ionic pores are the consequences of the presence of aggregates (lipopeptide aggregates or lipopeptide/phospholipid complex aggregates) in the phospholipid membrane. It has also been shown that, when active, iturins interact strongly with sterols, forming lipopeptide/cholesterol complexes. Therefore, the biologically efficient structures might be ternary structures: iturin/phospholipid/sterol (Maget-Dana and Peypoux 1994).