Bioconverstion of 7-Hydroxyflavanone: Isolation and Characterization of Twenty-One Phase I and Phase II Microbial Metabolites

Flavonoids are important polyphenolic phytochemicals abundant in fruits and vegetables and in many dietary supplements. The consumption of these compounds should be considered with caution when reflecting on their possible applications since they are known to interact with cytochromes P450 (CYPs) drug-metabolizing enzymes. From studies conducted over the last decade the bioactive forms may not necessarily be the naturally occurring forms, such as the aglycone or their glycosidic forms but instead the conjugates and metabolites [1,2]. Being predictive models for mammalian drug metabolism, microorganisms can be used to establish the metabolic fate and yield sufficient quantities of metabolites for structure analysis and further pharmacological evaluation [3]. Fermentation of 7-hydroxyflavanone (1) with fungal cultures Cunninghamella blakesleeana (ATCC 8688A) yielded (2–6). Mortierella zonata (ATCC 13309) inaddition to (2–3), produced metabolites (7–12). Beauveria bassiana (ATCC 7159) metabolized 1 to compounds (2, 3, 8 and 13–14). Chaetomium cochloides (ATCC 10195) yielded (2, 3, 9 & 15). Mucor ramannianus (ATCC 9628) transformed 1 to (7, 16–19). Aspergillus allaiceus (ATCC 10060) yielded metabolites (3, 16, 20–21). Metabolite 22 was produced by Rizopus oryzae (ATCC 11145). Structures of the metabolites were elucidated by means of spectroscopic data.

	R1	R2	R3	R4	R5
2	OSO3H	H	H	H	H
3	OH	H	H	OH	H
4	OH	OH	H	H	H
5	OSO3H	OH	H	H	H
6	OH	OSO3H	H	H	H
7	OSO3H	H	H	OH	H
10	OH	H	OH	H	H
11	OSO3H	H	OH	H	H
12	OH	H	OMe	H	H
13	glcMe	H	H	H	H
14	glcMe	H	OH	H	H
17	OH	H	H	OH	OH
18	deoxyallose	H	H	OH	H
19	OH	H	H	OH	OH
20	OH	H	OH	OH	H
21	OH	H	H	OSO3H	H
22	glc	H	H	H	H

	R1
8	OSO3H
15	OH

	R1
9	H
16	OH

Acknowledgements. This work was supported, in part by the United States Department of Agricultrue, Agricultural Research Specific Cooperative Agreement no. 58–6408–2-00009. References: [1] Walle T, Walgren RA, et al. “Flavonoids in Health and Disease.” Ed. By Rice-Evans E., Packer L., Marcel Dekker, Inc., New York, New York, 2003, pp. 349–358. [2] Wang MJ, Chao PL, et al. (2006)J of Food Drug Analysis 14: 247–53 [3] Clark AM, McChesney JD, et al. (1985) Med Res Rev 5: 231–253.