Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

Autor(es):Mostrar menos -

Tangerina, Marcelo M. P. ^[1] ; Furtado, Luciana Costa ^[2] ; Leite, Vida M. B. ^[3] ; Bauermeister, Anelize ^{[2, 4]} ; Velasco-Alzate, Karen ^[2] ; Jimenez, Paula C. ^[5] ; Garrido, Leandro M. ^[3] ; Padilla, Gabriel ^[3] ; Lopes, Norberto P. ^[4] ; Costa-Lotufo, Leticia V. ^[2] ; Pena Ferreira, Marcelo J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Bot, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Biomol, NPPNS, Ribeirao Preto, SP - Brazil

^[5] Univ Fed Sao Paulo, Inst Mar, Dept Ciencias Mar, Santos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 15, n. 12 DEC 21 2020.
• Citações Web of Science: 0

Resumo

Resorting to a One Strain Many Compounds (OSMAC) approach, the marine Streptomyces sp. BRB081 strain was grown in six different media settings over 1, 2, 3 or 7 days. Extractions of mycelium and broth were conducted separately for each media and cultivation period by sonication using methanol/acetone 1:1 and agitation with ethyl acetate, respectively. All methanol/acetone and ethyl acetate crude extracts were analysed by HPLC-MS/MS and data treatment was performed through GNPS platform using MZmine 2 software. In parallel, the genome was sequenced, assembled and mined to search for biosynthetic gene clusters (BGC) of secondary metabolites using the AntiSMASH 5.0 software. Spectral library search tool allowed the annotation of desferrioxamines, fatty acid amides, diketopiperazines, xanthurenic acid and, remarkably, the cyclic octapeptides surugamides. Molecular network analysis allowed the observation of the surugamides cluster, where surugamide A and the protonated molecule corresponding to the B-E isomers, as well as two potentially new analogues, were detected. Data treatment through MZmine 2 software allowed to distinguish that the largest amount of surugamides was obtained by cultivating BRB081 in SCB medium during 7 days and extraction of culture broth. Using the same data treatment, a chemical barcode was created for easy visualization and comparison of the metabolites produced overtime in all media. By genome mining of BRB081 four regions of biosynthetic gene clusters of secondary metabolites were detected supporting the metabolic data. Cytotoxic evaluation of all crude extracts using MTT assay revealed the highest bioactivity was also observed for extracts obtained in the optimal conditions as those for surugamides production, suggesting these to be the main active compounds herein. This method allowed the identification of compounds in the crude extracts and guided the selection of best conditions for production of bioactive compounds. (AU)

• Processo FAPESP: 17/16606-6 - Actinomicetos das ilhas do Brasil: uma abordagem metabolômica na bioprospecção de produtos naturais com potencial antitumoral
• Beneficiário: Marcelo Marucci Pereira Tangerina
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/17177-6 - Abordagem integrada na prospecção sustentável de produtos naturais marinhos: da diversidade a substâncias anticâncer
• Beneficiário: Leticia Veras Costa Lotufo
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 17/18235-5 - Potencial anticâncer de substâncias isoladas de Streptomyces SP. recuperada da Ascídia Euherdmania SP
• Beneficiário: Luciana Costa Furtado
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/17648-4 - Abordagem integrada na prospecção sustentável de produtos naturais marinhos: da diversidade a substâncias anticâncer
• Beneficiário: Anelize Bauermeister
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado