title: Transferring Fungi to a Deuterium-Enriched Medium Results in Assorted, Conditional Changes in Secondary Metabolite Production.
abstract: Deuterium is one of the few stable isotopes that have the capacity to significantly alter a compound's 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's characteristic isotope effects. Since the incorporation of deuterium into organic substrates is known to alter enzyme/protein-substrate 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 3-6 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's chemical diversity potential.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Park
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: King
authors.forename: Allison O
authors.initials: AO
authors.lastname: Mattes
authors.forename: Susan L
authors.initials: SL
authors.lastname: Nimmo
authors.forename: Chaevien
authors.initials: C
authors.lastname: Clendinen
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Edison
authors.affiliation: ⊥NMR Applications Support, Bruker Biospin Corporation, 15 Fortune Drive, Billerica, Massachusetts 01821, United States.
authors.forename: Clemens
authors.initials: C
authors.lastname: Anklin
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D001230:Aspergillus / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry; D003903:Deuterium; D005658:Fungi / Q000378:metabolism*; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification; D007553:Isotope Labeling; D055442:Metabolome; D055624:Methicillin-Resistant Staphylococcus aureus; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D001688:Biological Products; D026121:Indole Alkaloids; C000590722:brevianamide F; C539659:notoamide L; C470895:stephacidin A; D003903:Deuterium