Estudos de indução biossintética a partir de co-culturas microbianas em Penicillium sp.CML-3020
Data
2023-11-28
Autores
Rivero, Milena Patrícia Salgado 
Orientadores
Medeiros, Lívia Soman de
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Dada a busca contínua de agentes terapêuticos de origem natural, a exploração do metabolismo secundário de espécies Penicillium hoje representa um potencial promissor para novas descobertas. Neste contexto, investigações a respeito da quimiodiversidade de metabólitos produzidos por Penicillium sp.CML-3020, uma nova espécie isolada de Mata Atlântica foi o principal alvo de estudo desta pesquisa. Através da implementação de co-culturas de Penicillium sp.CML-3020 com outras espécies fúngicas e de seu cultivo de forma axênica, foi investigada a potencialidade da produção de metabólitos fúngicos bioativos. A investigação dos micro-extratos obtidos foi realizada pela análise de dados obtidos em cromatografia líquida de alta eficiência acoplada à espectrometria de massas de alta resolução (HPLC-DAD-HRMS). Através da inspeção de massas acuradas e consultas a bancos de dados de Produtos Naturais, foi realizada a desreplicação química dos compostos biossintetizados por Penicillium sp.CML-3020. A indução metabólica e um aumento significativo de alguns compostos foram observados quando esta especie foi submetido ao crescimento conjunto com Penicillium limosum, Penicillium setosum e Penicillium sp.CMLD-16, evidenciando assim a possível ativação de genes crípticos responsáveis pela codificação e síntese de metabólitos secundários produzidos por Penicillium sp.CML-3020. A partir do cultivo axênico para avaliação do perfil metabólico deste microorganismo, foram isoladas três substâncias identificadas como esclerodina (1), mistura epimérica de uma dicetoacetonilfenalenona (2) e derivado 9-desmetil de FR-901235 (3); que foram submetidos a ensaios antimicrobianos contra bactérias e fungos patogênicos em humanos.
Given the continuous search for therapeutic agents of natural origin, the exploration of the secondary metabolism of Penicillium species today represents a promising potential for new discoveries. In this context, investigations regarding the chemodiversity of metabolites produced by Penicillium sp.CML-3020, a new isolated species of Atlantic Mata was the main target of this research, through the implementation of co-cultures of Penicillium sp.CML-3020 with other fungal species and the cultivation of axenic form was investigated the potentiality of the production of novel bioactive fungal metabolites. The investigation of the obtained micro-extracts was performed by the analysis of data obtained in high performance liquid chromatography coupled to high resolution mass spectrometry (HPLC-DAD-HRMS). Through the inspection of accurate masses and consultations to databases of Natural Products, chemical dereplication of biosynthesis compounds by Penicillium sp.CML-3020. Metabolic induction and a significant increase of some compounds were observed when this specie was subjected to joint growth with Penicillium Limosum and Penicillium sp.CMLD-16, thus showing the possible activation of cryptic genes responsible for encoding and synthesis of secondary metabolites produced by Penicillium sp.CML-3020. From the fungic culture in axenic form of this microorganism, four substances were isolated, one of them identified as esclerodine, subsequently these compounds were submitted to cytotoxicity tests against leukemia cells and antimicrobial assays against bacteria and pathogenic fungi in humans. From the axenic culture to evaluate the metabolic profile of this microorganism, five substances were isolated, three of which have already been identified and will later be submitted antimicrobial assays against pathogenic bacteria and fungi in humans.
Given the continuous search for therapeutic agents of natural origin, the exploration of the secondary metabolism of Penicillium species today represents a promising potential for new discoveries. In this context, investigations regarding the chemodiversity of metabolites produced by Penicillium sp.CML-3020, a new isolated species of Atlantic Mata was the main target of this research, through the implementation of co-cultures of Penicillium sp.CML-3020 with other fungal species and the cultivation of axenic form was investigated the potentiality of the production of novel bioactive fungal metabolites. The investigation of the obtained micro-extracts was performed by the analysis of data obtained in high performance liquid chromatography coupled to high resolution mass spectrometry (HPLC-DAD-HRMS). Through the inspection of accurate masses and consultations to databases of Natural Products, chemical dereplication of biosynthesis compounds by Penicillium sp.CML-3020. Metabolic induction and a significant increase of some compounds were observed when this specie was subjected to joint growth with Penicillium Limosum and Penicillium sp.CMLD-16, thus showing the possible activation of cryptic genes responsible for encoding and synthesis of secondary metabolites produced by Penicillium sp.CML-3020. From the fungic culture in axenic form of this microorganism, four substances were isolated, one of them identified as esclerodine, subsequently these compounds were submitted to cytotoxicity tests against leukemia cells and antimicrobial assays against bacteria and pathogenic fungi in humans. From the axenic culture to evaluate the metabolic profile of this microorganism, five substances were isolated, three of which have already been identified and will later be submitted antimicrobial assays against pathogenic bacteria and fungi in humans.