Biotransformation of isoflavones by Aspergillus niger and Cunninghamella elegans

Abstract

Isoflavones are well-known flavonoids in many Legumes. Numerous biological activities are reported, including antioxidant, anti-inflamatory, anti-cancer, and antifungal activities. Their metabolic fates of natural isoflavones were studied in mammalians and several microorganisms. However, no detailed analyses have been reported on the isoflavone and its synthetic analogues. Recently, application of microorganism on natural products bioconversion has gained strong attentions due to their advantages over plants and animals. The metabolism of isoflavone and 4′-fluoroisoflavone were tested with Aspergillus niger and Cunninghamella elegans. The structures of selected metabolites were confirmed by synthetic standards. Both fungi rapidly transformed isoflavone into several metabolites. The half-lives of isoflavone (40 mg/L) were 1.6 and 4.2 days for A. niger and C. elegans, respectively. Overall, A. niger gave much more complex metabolite profiles. Approximately 23 metabolites were tentatively identified. The major metabolites were mono- and di-hydroxylated isoflavones at initial period, whereas those of 10 days were di- and tri-hydroxy-isoflavones. Hydroxylation usually occurred in B-ring of isoflavone, confirmed by authentic standards. Among dihydroxyisoflavones, 3′,4′-dihydroxy analogue was the most abundant metabolite, followed by daidzein (4′,7′-dihydroxyisoflavone). Methoxylated metabolites slowly accumulated during culturing. In addition, several glycosides were found, including hexose conjugates of mono-/di-hydroxyisoflavone and minor amount of pentose conjugates during culturing. However, 4′-fluoroisoflavone was not transformed during the culturing period, indicating the region-selective hydroxylation on initial metabolism of isoflavones.