Prealamethicin F50 and related peptaibols from Trichoderma arundinaceum: validation of their authenticity via in situ chemical analysis

Abstract

In the field of natural products chemistry, a common question pertains to the authenticity of an isolated compound, i.e. are the interesting side chains biosynthesized naturally or an artefact of the isolation/purification processes? The droplet-liquid microjunction-surface sampling probe (droplet-LMJ-SSP) coupled to a hyphenated system (UPLC-UV-HRESIMS) empowers the analysis of natural product sources in situ, providing data on the biosynthetic timing and spatial distribution of secondary metabolites. In this study the droplet-LMJ-SSP was utilized to validate the authenticity of two new peptaibols (2 and 3) as biosynthesized secondary metabolites, even though both them had structural features that could be perceived as artefacts. Compounds 2 and 3 were isolated from the scaled up fermentation of Trichoderma arundinaceum (strain MSX70741), along with a new member of the trichobrevin BIII complex (1), and four known compounds (4–7). The structures of the isolates were established using a set of spectroscopic and spectrometric methods, and their absolute configurations were determined by Marfey’s analysis. The cytotoxic activity of compounds 1, 3, 4 and 6 was evaluated against a panel of cancer cell lines, where cytotoxic activity in the single digit μM range was observed.

Characterizing the Pathogenic, Genomic, and Chemical Traits of Aspergillus fischeri , a Close Relative of the Major Human Fungal Pathogen Aspergillus fumigatus

“…fumigatus and A. fischeri led us to characterize the secondary metabolites produced by A. fischeri (Fig. S5) (46–50). The one strain-many compounds (OSMAC) approach was used to alter the secondary metabolites being biosynthesized in order to produce a diverse set of molecules (51–54).…”

Non-Volatile Metabolites from Trichoderma spp.

“…Compound 2 was the most active compound with IC 50 values ranging from 2.5 through 6.5 mM. Compound 3 exhibited moderate activity against HCT 116 and HT-29, with IC 50 values of 6.8 and 6.7 mM, respectively [3].…”

“…Trichoderma is a valuable resource for structurally novel natural products with diverse bioactivities [2]. Among well-studied fungi, Trichoderma species are known for their ability to produce bioactive secondary metabolites, including polyketides, alkaloids, terpenoids, and peptaibols [3]. Many species have been extensively investigated due to their application as biological control agents [4].…”

Drug Leads from Endophytic Fungi: Lessons Learned via Scaled Production

“…The droplet probe has been used to monitor the production of secondary metabolites in fungal cultures [25][26][27][28][29][30][31][32][33][34][35], with several notable examples highlighted in a recent review [16]. One benefit of this technique for this application was the ability to generate heat maps, showing in a relative manner where secondary metabolites are concentrated.…”