RESUMEN
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 IC50 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.
Asunto(s)
Antifúngicos/farmacología , Antineoplásicos/farmacología , Begoniaceae/microbiología , Peptaiboles/farmacología , Trichoderma/química , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Colletotrichum/efectos de los fármacos , Endófitos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Peptaiboles/química , Peptaiboles/aislamiento & purificación , Filogenia , Inhibidores de Proteasoma/farmacología , Trichoderma/clasificación , Trichoderma/genética , Trichoderma/aislamiento & purificaciónRESUMEN
Due to the increasing emergence of resistance of bacterial pathogens to current antibiotics, we have examined the marine fungi present in sea sediments obtained 200 m offshore to discover new antibacterial compounds active against multidrug-resistant bacteria. One strain, identified as Emericellopsis minima, was isolated from sediments of Talcahuano Bay (Chile). From the liquid culture of E. minima, we isolated Emerimicin IV, a unique fungal peptaibol that exhibited antibacterial activity. The structure of this compound was assigned by interpretation of 1H NMR and HR-LCMS data. Emerimicin IV showed bacteriostatic activity against clinical isolates of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis with MIC values ranging between 100 and 12.5 µg/mL.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Peptaiboles/química , Peptaiboles/farmacología , Antibacterianos/química , Ascomicetos/química , Bahías , Chile , Farmacorresistencia Bacteriana/efectos de los fármacos , Enterococcus faecalis/efectos de los fármacos , Sedimentos Geológicos/microbiología , Humanos , Espectroscopía de Resonancia Magnética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Vancomicina/farmacologíaRESUMEN
The Chilean Sepedonium aff. chalcipori strain KSH 883, isolated from the endemic Boletus loyo Philippi, was studied in a polythetic approach based on chemical, molecular, and biological data. A taxonomic study of the strain using molecular data of the ITS, EF1-α, and RPB2 barcoding genes confirmed the position of the isolated strain within the S. chalcipori clade, but also suggested the separation of this clade into three different species. Two new linear 15-residue peptaibols, named chilenopeptins A (1) and B (2), together with the known peptaibols tylopeptins A (3) and B (4) were isolated from the semisolid culture of strain KSH 883. The structures of 1 and 2 were elucidated on the basis of HRESIMS(n) experiments in conjunction with comprehensive 1D and 2D NMR analysis. Thus, the sequence of chilenopeptin A (1) was identified as Ac-Aib(1)-Ser(2)-Trp(3)-Aib(4)-Pro(5)-Leu(6)-Aib(7)-Aib(8)-Gln(9)-Aib(10)-Aib(11)-Gln(12)-Aib(13)-Leu(14)-Pheol(15), while chilenopeptin B (2) differs from 1 by the replacement of Trp(3) by Phe(3). Additionally, the total synthesis of 1 and 2 was accomplished by a solid-phase approach, confirming the absolute configuration of all chiral amino acids as l. Both the chilenopeptins (1 and 2) and tylopeptins (3 and 4) were evaluated for their potential to inhibit the growth of phytopathogenic organisms.
Asunto(s)
Antibacterianos/aislamiento & purificación , Peptaiboles/aislamiento & purificación , Secuencia de Aminoácidos , Antibacterianos/química , Antibacterianos/farmacología , Basidiomycota/metabolismo , Chile , Hypocreales/química , Estructura Molecular , Peptaiboles/química , Peptaiboles/farmacología , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/farmacología , Trichoderma/químicaRESUMEN
The fungal genus Trichoderma has various applications in industry and in medicine, and several species have economic importance as sources of enzymes, antibiotics, plant growth promoters, decomposers of xenobiotics, and as commercial biofungicides. Peptaibiotics and peptaibols are a class of linear peptides synthesized by such fungi, and more than 300 have been described to date. Of this class, those compounds exhibiting antimicrobial activity are referred to as antibiotic peptides. In this review, the biosynthesis, fermentation, structure elucidation (by MS and NMR techniques in particular) and biological activity of antibiotic peptides from Trichoderma species are described.