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 <i>N</i>-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 (<b>1</b>) and VIII (<b>2</b>) 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 (<b>1</b>) and VIII (<b>2</b>) by analysis of NMR data, along with an analysis by electronic circular dichroism and HRMS/MS data. Also, full genome sequencing and analysis of <i>Trichoderma</i> 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 <i>Plasmodium falciparum</i>.