Condensation of Macrocyclic Polyketides Produced by Penicillium sp DRF2 with Mercaptopyruvate Represents a New Fungal Detoxification Pathway

Autor(es):Mostrar menos -

de Castro, Marcos V. ^[1] ; Ioca, Laura P. ^[1] ; Williams, David E. ^{[2, 3]} ; Costa, Bruna Z. ^[4] ; Mizuno, Carolina M. ^{[1, 5, 6]} ; Santos, Mario F. C. ^[1] ; de Jesus, Karen ^[1] ; Ferreira, Everton L. F. ^[1] ; Seleghim, Mirna H. R. ^[5] ; Sette, Lara D. ^[7] ; Pereira Filho, Edenir R. ^[8] ; Ferreira, Antonio G. ^[8] ; Goncalves, Natalia S. ^[9] ; Santos, Raquel A. ^[9] ; Patrick, Brian O. ^[2] ; Andersen, Raymond J. ^{[2, 3]} ; Berlinck, Roberto G. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim Sao Carlos, CP 780, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1 - Canada

^[3] Univ British Columbia, Dept Earth Ocean & Atmospher Sci, Vancouver, BC V6T 1Z1 - Canada

^[4] Univ Estadual Campinas, Inst Quim, Caixa Postal 6154, BR-13083970 Campinas, SP - Brazil

^[5] Univ Fed Sao Carlos, Dept Ecol & Biol Evolut, Sao Carlos, SP - Brazil

^[6] Inst Pasteur, Dept Microbiol, Unit Mol Biol Gene Extremophiles, F-75015 Paris - France

^[7] Univ Estadual Paulista, Inst Biociencias, Dept Bioquim & Microbiol, Campus Rio Claro, Ave 24-A, BR-1515 Rio Claro, SP - Brazil

^[8] Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[9] Univ Franca, Lab Genet & Biol Mol, Ave Dr Armando Salles Oliveira, 201 Pq Univ, Franca, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Natural Products; v. 79, n. 6, p. 1668-1678, JUN 2016.
• Citações Web of Science: 11

Resumo

Application of a refined procedure of experimental design and chemometric analysis to improve the production of curvularin-related polyketides by a marine-derived Penicillium sp. DRF2 resulted in the isolation and identification of cyclothiocurvularins 6-8 and cyclosulfoxicurvularins 10 and 11, novel curvularins condensed with a mercaptolactate residue. Two additional new curvularins, 3 and 4, are also reported. The structures of the sulfur-bearing curvularins were unambiguously established by analysis of spectroscopic data and by X-ray diffraction analysis. Analysis of stable isotope feeding experiments with {[}U-(C3N)-C-13-N-15]-L-cysteine confirmed the presence of the 2-hydroxy-3-mercaptopropanoic acid residue in 6-8 and the oxidized sulfoxide in 10 and 11. Cyclothiocurvularins A (6) and B (7) are formed by spontaneous reaction between 10,11-dehydrocurvularin (2) and mercaptopyruvate (12) obtained by transamination of cysteine. High ratios of {[}U-(C3N)-C-13-N-15]-L-cysteine incorporation into cyclothiocurvularin B (7), the isolation of two diastereomers of cyclothiocurvularin, the lack of cytotoxicity of cyclothiocurvularin B (7) and its methyl ester (8), and the spontaneous formation of cyclothiocurvularins from 10,11-dehydrocurvularin and mercaptopyruvate provide evidence that the formation of cyclothiocurvularin may well correspond to a 10,11-dehydrocurvularin detoxification process by Penicillium sp. DRF2. (AU)

• Processo FAPESP: 13/50228-8 - Componentes da biodiversidade, e seus caracteres metabólicos, de ilhas do Brasil - uma abordagem integrada
• Beneficiário: Roberto Gomes de Souza Berlinck
• Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 10/50190-2 - Investigação do potencial biotecnológico e metabólico de organismos marinhos para processos de biorremediação e produção de substâncias com atividades anti-virais, anti-leishmania e anti-inflamatória (Biodiversidade Marinha)
• Beneficiário: Roberto Gomes de Souza Berlinck
• Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 05/60175-2 - Descoberta e desenvolvimento de potenciais agentes quimioterápicos a partir de invertebrados marinhos e de microrganismos associados
• Beneficiário: Roberto Gomes de Souza Berlinck
• Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 12/50026-3 - International collaboration in the chemistry of alkaloid natural product biosynthesis
• Beneficiário: Roberto Gomes de Souza Berlinck
• Linha de fomento: Auxílio à Pesquisa - Regular