1.D.115. The Pore-forming Fengycin (Fengycin) Family
Fengycin is an antifungal lipopeptide complex produced by Bacillus subtilis strain F-29-3. It inhibits filamentous fungi but is ineffective against yeast and bacteria. Inhibition is antagonized by sterols, phospholipids and oleic acid, whereas two other unsaturated fatty acids increase the antifungal effect (Vanittanakom et al. 1986). Fengycin consists of two main components differing by one amino acid exchange. Fengycin A is composed of 1 D-Ala, 1 L-Ile, 1 L-Pro, 1 D-allo-Thr, 3 L-Glx, 1 D-Tyr, 1 L-Tyr, 1 D-Orn, whereas in fengycin B the D-Ala is replaced by D-Val. The lipid moiety of both analogs is more variable, as fatty acids have been identified as anteiso-pentadecanoic acid (ai-C15), iso-hexadecanoic acid (i-C16), n-hexadecanoic acid (n-C16), and there is evidence for further saturated and unsaturated residues up to C18 (Vanittanakom et al. 1986).
The one-sided addition of fengycin (FE) to planar lipid bilayers mimicking target fungal cell membranes up to 0.1 to 0.5 muM in the membrane bathing solution leads to the formation of well-defined and well-reproducible single-ion channels of various conductances in the picosiemens range (Zakharova et al. 2019). FE channels were characterized by asymmetric conductance-voltage characteristics. Membranes treated with FE showed nonideal cationic selectivity in potassium chloride bathing solutions. The membrane conductance induced by FE increased with the second power of the lipopeptide aqueous concentration, suggesting that at least FE dimers are involved in the formation of conductive subunits. Pore formation was not distinctly affected by the molecular shape of membrane lipids but strongly depended on the presence of negatively charged species in the bilayer. FE channels showed weakly pronounced voltage gating. Small molecules known to modify the transmembrane distribution of electrical potential and the lateral pressure profile can modulate the channel-forming activity of FE. The observed effects of membrane modifiers were attributed to changes in lipid packing and lipopeptide oligomerization in the membrane (Zakharova et al. 2019).