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BIBTEX RIS

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

2016; American Chemical Society; Volume: 79; Issue: 6 Linguagem: Inglês

10.1021/acs.jnatprod.6b00295

1520-6025

Marcos V. de Castro, Laura P. Ióca, David E. Williams, Bruna Zucoloto da Costa, Carolina Megumi Mizuno, Mário F. C. Santos, Karen de Jesus, Éverton L. F. Ferreira, Mirna Helena Regali Seleghim, Lara Durães Sette, Edenir Rodrigues Pereira‐Filho, Antônio G. Ferreira, Natália S. Gonçalves, Raquel Alves dos Santos, Brian O. Patrick, Raymond J. Andersen, Roberto G. S. Berlinck,

Carbohydrate Chemistry and Synthesis

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–13C315N]-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–13C315N]-l-cysteine incorporation into cyclothiocurvularin B (7), the isolation of two diastereomers of cyclothiocurvularins, 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 cyclothiocurvularins may well correspond to a 10,11-dehydrocurvularin detoxification process by Penicillium sp. DRF2.