Novel peptide natural products from the NZ thermophilic microorganism Thermogemmatispora strain T81

Abstract

Genome mining of the newly described Thermogemmatispora strain T81, a thermophile from the Taupo Volcanic Zone, NZ, revealed the potential to produce novel ribosomally synthesised and post-translationally modified peptide natural products. Previous work established that strain T81 exhibits antimicrobial activity against a wide range of extremophilic bacteria. This thesis describes the mass spectrometry-guided screening of strain T81, and the subsequent isolation and structure elucidation of a novel lanthipeptide, tikitericin (32). Tikitericin is a class II lanthipeptide which bears no sequence homology to known lanthipeptides. Comprised of 35 amino acids, the three-dimensional structure of tikitericin is conformationally restricted by four macrocyclic structures formed by the non-proteinogenic residues methyllanthionine and lanthionine. The amino acid sequence, predicted through bioinformatic analysis, was confirmed by chemical degradation experiments and subsequent tandem mass spectrometry. Characterisation of tikitericin’s ring topology was performed by tandem mass spectrometry and stereochemical configuration of the (methyl)lanthionine residues was determined by gas chromatography mass spectrometry.