NMR Analysis and Assignment of a Biosynthesis Gene Cluster for Trichokonins VI and VIII, Antiplasmodial Large Peptaibols Produced by a Trichoderma sp. Fungus

Abstract

Peptaibols are modified linear peptides that typically include an acyl fragment connected at the N-terminal moiety, a reduced acid extremity and α-aminoisobutyric acid residues as common features, as well as other structural modifications. Peptaibols very often display potent biological activity, in particular, antimicrobial activity. Trichokonins VI (1) and VIII (2) are large peptaibols composed of 20 amino acids, which were previously only characterized by analysis of MS/MS data. We herein report the first full characterization of trichokonins VI (1) and VIII (2) by analysis of NMR data, along with an analysis by electronic circular dichroism and HRMS/MS data. Also, full genome sequencing and analysis of Trichoderma sp. L2-2 allowed us to identify a peptaibol biosynthesis gene cluster and the proposal for a biosynthetic assembly of trichokonins VI and VIII. Trichokonins VI and VIII also demonstrated antiplasmodial activity at the submicromolar range against Plasmodium falciparum.