Transferring Fungi to a Deuterium-Enriched Medium Results in Assorted, Conditional Changes in Secondary Metabolite Production

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• 作者：Bin Wang ; Elizabeth M. Park ; Jarrod B. King ; Allison O. Mattes ; Susan L. Nimmo ; Chaevien Clendinen ; Arthur S. Edison ; Clemens Anklin ; Robert H. Cichewicz
• 刊名：Journal of Natural Products
• 出版年：2015
• 出版时间：June 26, 2015
• 年：2015
• 卷：78
• 期：6
• 页码：1415-1421
• 全文大小：287K
• ISSN：1520-6025

文摘

Deuterium is one of the few stable isotopes that have the capacity to significantly alter a compound鈥檚 chemical and biological properties. The addition of a single neutron to a protium atom results in the near doubling of its mass, which gives rise to deuterium鈥檚 characteristic isotope effects. Since the incorporation of deuterium into organic substrates is known to alter enzyme/protein鈥搒ubstrate interactions, we tested the extent to which deuterium enrichment would modify fungal secondary metabolite production. Several fungal cultures were tested, and in all cases their secondary metabolomes were marked by changes in natural product production. Workup of one Aspergillus sp. grown under deuterium-enrichment conditions resulted in the production of several secondary metabolites not previously detected from the fungus. Bioassay testing revealed that in comparison to the inactive crude fungal extract derived from growing the fungus under non-deuterium-enriched conditions, an extract derived from the same isolate cultured in a deuterium-enriched medium inhibited methicillin-resistant Staphylococcus aureus. Using an assortment of NMR and mass spectrometry experiments, we were able to identify the bacterial inhibitor as an isotope-labeled version of pigmentosin A (6). Five additional isotopically labeled metabolites were also obtained from the fungus including brevianamide F (1), stephacidin A (2), notoamide D (3), notoamide L (4), and notoamide C (5). Given the assorted changes observed in the secondary metabolite profiles of this and other fungi grown in deuterium-enriched environments, as well as the fact that 1 and 3鈥?b>6 had not been previously observed from the Aspergillus sp. isolate used in this study, we propose that deuterium enrichment might offer an effective method for further expanding a fungus鈥檚 chemical diversity potential.