Departamento de Ciências Exatas, Universidade de São Paulo, Escola Superior de Agricultura "Luiz de Queiroz", CP 9, Piracicaba, SP, 13418-900, Brasil.
Centro Nacional de Pesquisa em Energia e Materiais, Laboratório Nacional de Biociências, CP 6192, Campinas, SP, 13083-970, Brasil.
Braz J Microbiol. 2020 Sep;51(3):989-997. doi: 10.1007/s42770-020-00270-9. Epub 2020 Apr 24.
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 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.
木霉属真菌是产生具有多种应用的次级代谢产物的著名生产者，例如具有抗菌、抗真菌和促进植物生长的特性。肽抗生素是此类真菌产生的线性肽，迄今为止已描述了超过 440 种化合物，包括 Tricholongins、Longibrachins、Trichobrachins 和 Trichovirins。肽抗生素由非核糖体肽合成酶合成，具有多种生物活性。我们的研究小组从内生真菌 Begonia venosa 中的 Trichoderma sp. P8BDA1F1 中分离出四种具有抗真菌活性的肽抗生素（6DP2、6DP3、6DP4 和 6DP5），可对抗植物病原体炭疽菌和蛋白酶体（癌症化疗靶标）。该内生真菌的乙酸乙酯提取物对 C. gloeosporioides 和蛋白酶体的活性分别为 6.01%和 75%。通过 MS/MS 鉴定分离出的化合物，并与文献数据进行比较，表明存在含有 20 个氨基酸残基的 Trilongins BI、BII、BIII 和 BIV 肽抗生素。Trilongin BI 对 C. gloeosporioides 的最小抑菌浓度为 40 μM，Trilongin BII 为 320 μM，Trilongin BIII 为 160 μM，Trilongin BIV 为 310 μM。BI-BIV Trilongins 抑制蛋白酶体 ChTL 活性，IC 值分别为 6.5 ± 2.7；4.7 ± 1.8；6.3 ± 2.2；和 2.7 ± 0.5 μM。这些化合物在体外测试了对利什曼原虫（L.）婴儿体内的阿米巴原虫，但没有表现出选择性。这是首次报道具有抗 C. gloeosporioides 和蛋白酶体靶标活性的 Trilongins BI-BIV。
