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Title: Binding of furanocoumarins in grapefruit juice to Aspergillus niger hyphae

item Myung, Kyung
item Manthey, John
item Narciso, Jan

Submitted to: Applied Microbiology and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2007
Publication Date: 2/14/2008
Citation: Myung, K., Manthey, J.A., Narciso, J.A. 2008. Binding of furanocoumarins in grapefruit juice to Aspergillus niger hyphae. Applied Microbiology and Biotechnology. 78:401-407.

Interpretive Summary: Furanocoumarins (FCs), found in grapefruit, have been shown to be involved in "grapefruit-drug interactions" by inhibiting the cytochrome P450 3A4 (CYP 3A4) activity an enzyme in the digestive tract responsible for metabolism of certain drugs. In this study, we reported a capability of Aspergillus niger (food grade fungus) in adsorbing FCs in grapefruit juice (GFJ). We carried out fermentation experiments using GFJ and A. niger. From the fermentation, we found that most of polar FCs were disappeared in GFJ for 4 days, leading to a question if the FCs were actively transported in the fungus. Interestingly, most of disappeared FCs was found to be adsorbed to the autoclaved (heat-killed) fungal material. The level of the FCs removal was proportional to the amount of autoclaved fungus we added in GFJ. We also tested the CYP 3A4 enzyme inhibition by autoclaved fungus-treated GFJ and found 65% reduction compared to non-treated GFJ when we added 3 g autoclaved fungal mass. The reduction occurred because autoclaved fungus adsorbed nonpolar FCS in GFJ, but some polar FCs, which were not adsorbed by the autoclaved fungus, could be responsible for the remaining inhibition. Our results would be helpful in understanding the interaction of the fungus with FCs and providing a possible industrial application for FCs-reduced GFJ production.

Technical Abstract: Furanocoumarins (FCs), a class of aromatic compounds, are important due to their biological activities and clinical applications. The FCs in grapefruit are involved in the "grapefruit/drug interactions", in which the FCs inhibit the cytochrome P450 3A4 (CYP 3A4) activity responsible for metabolism of certain drugs. These interactions have created a need to remove the FCs from grapefruit juice (GFJ) in a manner that retains much of the original juice sensory attributes. In our current experiments, grapefruit juice was incubated with Aspergillus niger, and compositional changes in flavanones, furanocoumarins, and other phenolic compounds were monitored. Uptake of polar hydroxycinnamates, flavonoid glycosides, and a few polar FCs by A. niger did not occur, while the non-polar FCs and 7-geranyloxycoumarin were efficiently taken up by the fungal tissue. This biosorption was also observed with autoclaved fungus, indicating that the uptake of non-polar FCs by A. niger hyphae was due to adsorption rather than metabolism. The binding of the FCs to autoclaved fungus was completed within 4 hr and the level of binding was proportional to the amount of autoclaved fungal mass used. As expected, the removal of the FCs from GFJ by autoclaved fungus led to a reduced inhibition of CYP 3A4 activity by both GFJ and GFJ extracts.