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

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, nove...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of natural products (Washington, D.C.) Vol. 79; no. 6; pp. 1668 - 1678
Main Authors:	de Castro, Marcos V, Ióca, Laura P, Williams, David E, Costa, Bruna Z, Mizuno, Carolina M, Santos, Mario F. C, de Jesus, Karen, Ferreira, Éverton L. F, Seleghim, Mirna H. R, Sette, Lara D, Pereira Filho, Edenir R, Ferreira, Antonio G, Gonçalves, Natália S, Santos, Raquel A, Patrick, Brian O, Andersen, Raymond J, Berlinck, Roberto G. S
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society and American Society of Pharmacognosy 24-06-2016
Subjects:	Crystallography, X-Ray Cysteine Drug Screening Assays, Antitumor Marine Biology Molecular Structure Nuclear Magnetic Resonance, Biomolecular Penicillium - chemistry Polyketides - chemistry Polyketides - isolation & purification Polyketides - pharmacology Stereoisomerism Zearalenone - analogs & derivatives Zearalenone - chemistry
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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–13C3 15N]-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–13C3 15N]-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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0163-3864 1520-6025
DOI:	10.1021/acs.jnatprod.6b00295