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

  • Biotechnology and Industrial Microbiology - Research Paper
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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 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.

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Acknowledgments

We thank AZN Fernandes for enzyme preparation and LQPN, LBE, LPP, and LEC for facilities (LNBio, CNPEM). We thank Dr. Roberto G. de S. Berlinck for the equipment and support, Dr. Marco A. de Assis and Dr. Eliane Jacques for plant identification, Marta L.Lima by performing the ex vivo assay against the intracellular amastigotes of L. infantum, and Instituto Chico Mendes and Ibama for helping with plant collections in the Island. SISBio authorization under an accession number (37256-4) and at Sisgen by the code A046A6C.

Funding

Financial support was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (grants 2014/15760-3 and 2014/10753-9) and BIOTA/BIOprospecTA FAPESP (grant 2013/50228-8). Scholarships to Diana F. Grigoletto (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 88881.133610/2016-01 and Conselho Nacional de Desenvolvimento Científico e Tecnológico 142079/2016-2) and Ana M. Correia (FAPESP: 2014/12021-5) are also gratefully recognized.

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Authors and Affiliations

  1. Departamento de Ciências Exatas, Universidade de São Paulo, Escola Superior de Agricultura “Luiz de Queiroz”, CP 9, Piracicaba, SP, 13418-900, Brasil

    Diana F. Grigoletto & Simone P. Lira

  2. Centro Nacional de Pesquisa em Energia e Materiais, Laboratório Nacional de Biociências, CP 6192, Campinas, SP, 13083-970, Brasil

    Daniela B. B. Trivella

  3. Instituto Adolfo Lutz, Centro de Parasitologia e Micologia, São Paulo, SP, 01246-000, Brasil

    André G. Tempone

  4. Departamento de Biologia Geral e Aplicada, Universidade Estadual Paulista (UNESP), Rio Claro, SP, 13506-900, Brasil

    André Rodrigues & Ana Maria L. Correia

  5. Centro de Estudos de Insetos Sociais, Universidade Estadual Paulista (UNESP), Rio Claro, SP, 13506-900, Brasil

    André Rodrigues

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  1. Diana F. Grigoletto
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  2. Daniela B. B. Trivella
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  4. André Rodrigues
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  5. Ana Maria L. Correia
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  6. Simone P. Lira
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Correspondence to Simone P. Lira.

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The Ethics Committee on Animal Research approved the project (number CEUA IAL/Pasteur 02/2011), according to the “Guide to the Care and Use of Laboratory Animals” of the National Academy of Sciences.

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Grigoletto, D.F., Trivella, D.B.B., Tempone, A.G. et al. Antifungal compounds with anticancer potential from Trichoderma sp. P8BDA1F1, an endophytic fungus from Begonia venosa. Braz J Microbiol 51, 989–997 (2020). https://doi.org/10.1007/s42770-020-00270-9

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