Title | Tolypocladamide H and the Proposed Tolypocladamide NRPS in Species. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Tehan RM, Blount RR, Goold RL, Mattos DR, Spatafora NR, Tabima JF, Gazis R, Wang C, Ishmael JE, Spatafora JW, McPhail KL |
Journal | J Nat Prod |
Volume | 85 |
Issue | 5 |
Pagination | 1363-1373 |
Date Published | 2022 05 27 |
ISSN | 1520-6025 |
Keywords | Animals, 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. |
DOI | 10.1021/acs.jnatprod.2c00153 |
Alternate Journal | J Nat Prod |
PubMed ID | 35500108 |
PubMed Central ID | PMC9150700 |