Bioactive secondary metabolites produced by filamentous fungi from extreme environments

Author(s)

Darlon Irineu Bernardi

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT)
• Defense date: 2023-05-09

Examining board members

Eder Tadeu Gomes Cavalheiro; Fernanda Oliveira das Chagas; Antonio Aprigio da Silva Curvelo; Maria Helena Sarragiotto; Maria Fatima das Graças Fernandes da Silva

• Advisor: Roberto Gomes de Souza Berlinck

Abstract

The diversity of secondary bioactive metabolites produced by microorganisms in culture medium is expressive. However, over the last few decades, the investigation of water-soluble secondary metabolites, as well as the study of microbial strains from unconventional environments, has been abandoned. This work aimed to investigate the cultivation conditions of endophytic fungi and soil isolates, showing optimal conditions for growth and metabolic production. Subsequently, biological and chemical screening of fractions from extracts obtained from the culture medium of selected strains was carried out, as well as the isolation of water-soluble and lipophilic bioactive metabolites produced by these strains. Two strains of filamentous fungi were cultivated on a larger scale: an endophytic fungus isolated from the plant Anthurium alcatrazense, classified as Byssochlamys spectabilis Aa1 and produced two new secondary metabolites, the diketopiperazine cyclo-(D-Trp-L-Glu) and the peptide derivative formyl-L-tryptophyl-L-alanine, in addition to the known compound N-acetyl-kynurenine, which had its NMR data and absolute configuration established as (S)-N-acetyl-kynurenine. The compounds cyclo-(D-Trp-L-Glu) and (S)-N-acetyl-kynurenine were evaluated against OVCAR-3 cells and showed IC50 of 1.120 and 1.073 µM, respectively. The second strain cultived in large scale, the fungus Aspergillus sp. SDC28 isolated from cave soil, produced in its culture medium two lipophilic compounds, versicolorin C and versiconol. Their anticancer potential against OVCAR-3 cells were also determined with IC50 of 0.24 and 1.07 µM, respectively. These compounds had their absolute configuration determined. In order to know the selectivity power of the mixture of XAD-2,-4,-7 resins during the process of water-soluble metabolites adsorption, the natural product solitumine A produced by the fungal strain Penicillium solitum IS1-A was used. The capture of solitumine A through the adsorptive resins allowed us to avaliate with which individual resin its chemical structure have greater affinity. (AU)

• FAPESP's process: 16/21341-9 - Hydrophilic and bioactive secondary metabolites produced by filamentous fungi
• Grantee: Darlon Irineu Bernardi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)