Isolation and structural elucidation of the 11-residue peptaibol antibiotic, harzianin HK VI

Abstract

Harzianin HK VI, one of the major peptides of the natural mixture of peptaibol antibiotics biosynthesized by the fungus Trichoderma pseudokoningii, has been isolated by a multi-step chromatography procedure including HPLC. Its sequence was determined by positive ion FAB MS and two-dimensional ¹H and ¹³C NMR experiments (COSY, HOHAHA, HSQC-HOHAHA, HMBC), allowing the location in the sequence of two isoleucines at positions 3 and 4 and of two leucines at positions 7 and 8, which could not be distinguished on the basis of their ¹H NMR spin systems. Harzianin HK VI is an 11-residue peptaibol with two Aib-Pro sequences at positions 5–6 and 9–10. From ROESY data and amide temperature coefficients, a β-bend ribbon stabillised by intramolecular hydrogen bonds of the 4→1 type is suggested. Despite the short sequence, harzianin HK VI increases the permeability of liposome bilayers to the same extent as longer 14-residue peptaibols.