TitleTolypocladamide H and the Proposed Tolypocladamide NRPS in Species.
Publication TypeJournal Article
Year of Publication2022
AuthorsTehan RM, Blount RR, Goold RL, Mattos DR, Spatafora NR, Tabima JF, Gazis R, Wang C, Ishmael JE, Spatafora JW, McPhail KL
JournalJ Nat Prod
Volume85
Issue5
Pagination1363-1373
Date Published2022 05 27
ISSN1520-6025
KeywordsAnimals, Chromatography, Liquid, Cyclosporins, Mammals, Molecular Structure, Multigene Family, Peptaibols, Tandem Mass Spectrometry
Abstract

The genome of entomopathogenic fungus Gams encodes 43 putative biosynthetic gene clusters for specialized metabolites, although genotype-phenotype linkages have been reported only for the cyclosporins and fumonisins. was cultured in defined minimal media, supplemented with or without one of nine different amino acids. Acquisition of LC-MS/MS data for molecular networking and manual analysis facilitated annotation of putative known and unknown metabolites. These data led us to target a family of peptaibols and guided the isolation and purification of tolypocladamide H (), which showed modest antibacterial activity and toxicity to mammalian cells at micromolar concentrations. HRMS/MS, NMR, and advanced Marfey's analysis were used to assign the structure of as a peptaibol containing 4-[()-2-butenyl]-4-methyl-l-threonine (Bmt), a hallmark structural motif of the cyclosporins. LC-MS detection of homologous tolypocladamide metabolites and phylogenomic analyses of peptaibol biosynthetic genes in other cultured species allowed assignment of a putative tolypocladamide nonribosomal peptide synthetase gene.

DOI10.1021/acs.jnatprod.2c00153
Alternate JournalJ Nat Prod
PubMed ID35500108
PubMed Central IDPMC9150700