Antifungal compounds with anticancer potential from Trichoderma sp. P8BDA1F1, an endophytic fungus from Begonia venosa

Abstract

Fungi in the genus Trichoderma are notorious producers of secondary metabolites with diverse applications, such as antibacterial, antifungal, and plant growth-promoting properties. Peptaibols are linear peptides produced by such fungi, with more than 440 compounds described to date, including tricholongins, longibrachins, trichobrachins, and trichovirins. Peptaibols are synthesized by non-ribosomal peptide synthetases and they have several biological activities. Our research group isolated four peptaibols (6DP2, 6DP3, 6DP4, and 6DP5) with antifungal activity against the plant pathogen Colletotrichum gloeosporioides and the proteasome (a cancer chemotherapy target) from Trichoderma sp. P8BDA1F1, an endophytic fungus from Begonia venosa. The ethyl acetate extract of this endophyte showed activity of 6.01% and 75% against C. gloeosporioides and the proteasome, respectively. The isolated compounds were identified by MS/MS and compared to literature data, suggesting the presence of trilongins BI, BII, BIII, and BIV, which are peptaibols containing 20 amino acid residues. The minimum inhibitory concentration against C. gloeosporioides was 40 μM for trilongin BI, 320 μM for trilongin BII, 160 μM for trilongin BIII, and 310 μM for trilongin BIV. BI-BIV trilongins inhibited proteasome ChTL activity, with IC 50 values of 6.5 ± 2.7; 4.7 ± 1.8; 6.3 ± 2.2; and 2.7 ± 0.5 μM, respectively. The compounds were tested ex vivo against the intracellular amastigotes of Leishmania (L.) infantum but showed no selectivity. It is the first report of trilongins BI-BIV with antifungal activity against C. gloeosporioides and the proteasome target.

Enhancing the Discovery of Bioactive Secondary Metabolites From Fungal Endophytes Using Chemical Elicitation and Variation of Fermentation Media

“…Mycotoxins such as fumonisin B1 and fumonisin A1 in addition to one other known metabolite: glisoprenin E were dereplicated from two Fusarium strains ( Supplementary Table S2 ). The exact identification of several of these compounds was performed by HR-LCMS/MS comparison with our in-house authentic standard compounds library or with MS/MS spectra reported in the literature ( Tamura et al, 2014 ; Grigoletto et al, 2020 ).…”

Longibrachiamide A, a 20‐Residue Peptaibol Isolated from Trichoderma longibrachiatum Rifai DMG‐3‐1‐1

“…But the further isolated peptaibols with 20 residues showed stronger cytotoxic activities against MCF‐7, BV2, A549 cells and stronger antibacterial activities against Gram‐positive bacteria including the methicillin‐resistant Staphylococcus aureus MRSA T144, Staphylococcus aureus ATCC 29213 and vancomycin resistant Enterococcus faecium VRE‐10. Peptaibols with 20 residues had been isolated from several fungi, [10–18,20] but the 14 th residues of all the reported compounds were Pro residues, Hyp as the 14 th residue in compound 1 was reported for the first time. Peptaibols were usually identified by ESI‐MS/MS, but some residues could not be identified definitely, such as Leu/Ile, Val/Iva, Leuol/Ileol, and Valol/Ivaol.…”

“…[2 -9] 20-Residue peptaibols had been isolated from several fungi, such as Trichoderma koningii, [10,11] Trichoderma atroviride, [12] Trichoderma parceramosum, [13] Hypocrea pulvinata, [14] Trichoderma arundinaceum, [15] Trichoderma orientale, [16] and some other fungi of Trichoderma genus. [17,18] compounds 2-4 were also reported for the first time. The ECD spectra of 1-4 revealed that they all had mixed 3 10 -/α-helical conformations.…”

“…Peptaibols were characterized by C‐amino alcohol terminus, N‐acyl terminus and a high proportion of nonproteinogenic amino acids such as α ‐aminoisobutyric acid (Aib) or isovaline (Iva) [2–9] . 20‐Residue peptaibols had been isolated from several fungi, such as Trichoderma koningii , [10,11] Trichoderma atroviride , [12] Trichoderma parceramosum , [13] Hypocrea pulvinata , [14] Trichoderma arundinaceum , [15] Trichoderma orientale , [16] and some other fungi of Trichoderma genus [17,18] . Peptaibols with 20 residues showed extensive bioactivities, such as Ca 2+ channel agonist, [10] membrane‐perturbing activity, [12] cytotoxic activity, [15,18] antifungal activity, [16] and proteasome inhibition activity [17] …”

Fungal Guttation, a Source of Bioactive Compounds, and Its Ecological Role—A Review

“…As the peptaibols family is structurally diverse, trichokonin subclasses have been investigated as well [ 96 ]. Anticancer activity against selected cell lines showed also: culicinin D on breast tumor cells [ 97 ], alamethicin F50 derivative on a panel of cancer lines [ 60 ], emericellipsin on HepG2 [ 98 ], and potentially trilongins, as proteasome inhibitors [ 99 ]. It is worth noticing that members of different peptaibol subclasses have been found in fungal exudates [ 19 ].…”