Biotransformation of the soy isoflavone genistein by sequential 3'-hydroxylation using recombinant Escherichia coli expressing tyrosinase from Bacillus megaterium and then methylation using another recombinant E. coli expressing O -methyltransferase from Streptomyces peucetius was conducted. The results showed that two metabolites were produced from the biotransformation, identified as 5,7,4'-trihydroxy-3'-methoxyisoflavone and 5,7,3'-trihydroxy-4'-methoxyisoflavone, respectively, based on their mass and nuclear magnetic resonance spectral data. 5,7,4'-Trihydroxy-3'-methoxyisoflavone showed potent antiproliferative activity toward mouse B16 melanoma cells with an IC 50 value of 68.8 μM. In contrast, the compound did not show any cytotoxicity toward mouse normal fibroblast cells, even at 350 μM concentration. The results of the present study offer insight on the production of both 5,7,4'-trihydroxy-3'-methoxyisoflavone and 5,7,3'-trihydroxy-4'-methoxyisoflavone by two recombinant E. coli strains and the potential anti-melanoma applications of 5,7,4'-trihydroxy-3'-methoxyisoflavone.

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Daidzein and genistein are two major components of soy isoflavones. They exist abundantly in plants and possess multiple bioactivities. In contrast, ortho-hydroxydaidzein (OHD) and ortho-hydroxygenistein (OHG), including 6-hydroxydaidzein (6-OHD), 8-hydroxydaidzein (8-OHD), 3'-hydroxydaidzein (3'-OHD), 6-hydroxygenistein (6-OHG), 8-hydroxygenistein (8-OHG), and 3'-hydroxygenistein (3'-OHG), are rarely found in plants. Instead, they are usually isolated from fermented soybean foods or microbial fermentation broth feeding with soybean meal. Accordingly, the bioactivity of OHD and OHG has been investigated less compared to that of soy isoflavones. Recently, OHD and OHG were produced by genetically engineering microorganisms through gene cloning of cytochrome P450 (CYP) enzyme systems. This success opens up bioactivity investigation and industrial applications of OHD and OHG in the future. This article reviews isolation of OHD and OHG from non-synthetic sources and production of the compounds by genetically modified microorganisms. Several bioactivities, such as anticancer and antimelanogenesis-related activities, of OHD and OHG, are also discussed.

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Principal rotenoids (deguelin, tephrosin, rotenone, and 12a-hydroxyrotenone) (3-30microM) isolated from the stems of Erycibe expansa significantly inhibited invasion of human fibrosarcoma HT1080 cells through Matrigel-coated filters and release of proMMPs-2 and 9. In addition, deguelin and tephrosin showed differentiation-inducing activity in human promyelocytic leukemia HL-60 cells. Furthermore, effects of various constituents isolated from the ethyl acetate-soluble fraction on proliferation of human leukemia U937 cells were examined. As a result, most of isoflavones and several flavans as well as rotenoids showed moderate or substantial anti-proliferative activities.

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A new flavanol, erycibenin D, and two new flavans, erycibenins E and F, were isolated from the stems of Erycibe expansa originating in Thailand. The structures of new flavonoids were elucidated on the basis of chemical and physicochemical evidence. In addition, the inhibitory activities of the isolated constituents from E. expansa on lipopolysaccharide-activated nitric oxide production in mouse peritoneal macrophages were examined. Among the principal constituents, two isoflavones, clycosin (IC50 = 13 microM) and erythrinin B (18 microM), and two rotenoids, deguelin (26 microM) and rotenone (27 microM), were found to show potent inhibitory activity.

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The methanolic extract from the stems of Erycibe expansa was found to show a hepatoprotective effect on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes. By bioassay-guided separation, two new prenylisoflavones and a pterocarpane, erycibenins A (1), B (2), and C (3), were isolated from the active fraction (the EtOAc-soluble fraction) together with ten isoflavones (4-13) and seven pterocarpanes (14-20). The stereostructures of the new compounds were determined on the basis of chemical and physicochemical evidence including modified Mosher's method. In addition, the isolated constituents, erycibenin A (1, IC50 = 79 microM), genistein (6, 29 microM), orobol (7, 36 microM), and 5,7,4'-trihydroxy-3'-methoxyisoflavone (8, 55 microM) exhibited inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.

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