Combining UHPLC-High Resolution MS and Feeding of Stable Isotope Labeled Polyketide Intermediates for Linking Precursors to End Products

We present the results from stable isotope labeled precursor feeding studies combined with ultrahigh performance liquid chromatography-high resolution mass spectrometry for the identification of labeled polyketide (PK) end-products. Feeding experiments were performed with 13C8-6-methylsalicylic acid...

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Bibliographic Details
Published in:Journal of natural products (Washington, D.C.) D.C.), 2015-07, Vol.78 (7), p.1518-1525
Main Authors: Klitgaard, Andreas, Frandsen, Rasmus J. N, Holm, Dorte K, Knudsen, Peter B, Frisvad, Jens C, Nielsen, Kristian F
Format: Article
Language:English
Subjects:
Algorithms
Aspergillus - chemistry
Fusarium - chemistry
Isotope Labeling
Molecular Structure
Patulin - chemistry
Polyketides - chemistry
Pyrones - chemistry
Quinones - chemistry
Salicylates - chemistry
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Summary:We present the results from stable isotope labeled precursor feeding studies combined with ultrahigh performance liquid chromatography-high resolution mass spectrometry for the identification of labeled polyketide (PK) end-products. Feeding experiments were performed with 13C8-6-methylsalicylic acid (6-MSA) and 13C14-YWA1, both produced in-house, as well as commercial 13C7-benzoic acid and 2H7-cinnamic acid, in species of Fusarium, Byssochlamys, Aspergillus, and Penicillium. Incorporation of 6-MSA into terreic acid or patulin was not observed in any of six evaluated species covering three genera, because the 6-MSA was shunted into (2Z,4E)-2-methyl-2,4-hexadienedioic acid. This indicates that patulin and terreic acid may be produced in a closed compartment of the cell and that (2Z,4E)-2-methyl-2,4-hexadienedioic acid is a detoxification product toward terreic acid and patulin. In Fusarium spp., YWA1 was shown to be incorporated into aurofusarin, rubrofusarin, and antibiotic Y. In A. niger, benzoic acid was shown to be incorporated into asperrubrol. Incorporation levels of 0.7–20% into the end-products were detected in wild-type strains. Thus, stable isotope labeling is a promising technique for investigation of polyketide biosynthesis and possible compartmentalization of toxic metabolites.
ISSN:0163-3864
1520-6025
DOI:10.1021/np500979d