# Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review
## 3 Microbiological Transformation of Isoflavonoids and Flavonoids
### Biotransformation of Isoflavones and Flavonoids by Fungi
Twenty-three metabolites were preliminarily identified during the biotransformation of _A. niger_. In the early stage, the main metabolites were mono-hydroxyl and dihydroxyl isoflavones, and after 10 days, the main metabolites were dihydroxyl and trihydroxyl isoflavones. The hydroxylation of isoflaves usually occurs in the B ring. Among them, 3',4'-dihydroxy analogues were the most abundant. Methoxy metabolites accumulate slowly during culture. In addition, some glycosides have been detected. However, 4'-fluoroisoflavones were not transformed during culture, indicating that there was regional selective hydroxylation in the initial metabolism of isoflaves [78]. \(\alpha\)-Naphthoflavone (7,8-benzoflavone) (**137**) and \(\beta\)-naphthoflavone (5,6-benzoflavone) (**139**) were transformed by _Aspergillus glaucus_ AM 211, _A. niger_ UPF 724, _Penicillium thomi_ AM 91, _Cladosporium aellaneum_ AM 135, and _Verticillium_ sp. AM 424 via \(O\)-demethylation and hydroxylation. The substrate \(\alpha\)-NF was metabolized in seven days to produce 4\({}^{\prime}\)-hydroxy-\(\alpha\)-naphthoflavone (**141**) and 4\({}^{\prime}\)-hydroxy-\(\beta\)-naphthoflavone (**142**). The most effective biocatalysts were two strains of AM 211 and AM 424, which converted **137** to **141** with the rates of 43% and 63%, respectively. Among them, only three strains AM 135, AM 424, and AM 211 can transform \(\beta\)-NF (**139**) into compounds **141** and **142**. Besides, 4\({}^{\prime}\)-methoxy-\(\alpha\)-NF (**138**), a derivative of naphthoflavone, was transformed to compound **141** by _A. niger_ UPF 724 and _P. thomi_ AM 91, and the derivative 4\({}^{\prime}\)-methoxy-\(\beta\)-NF (**140**) was transformed to compound **142** by _A. niger_ UPF 724 [79]. Bavachinin (**143**) was transformed in the broth of _Cunningham blakesleeana_ AS 3.0970 to 4\({}^{\prime}\)-hydroxybavachinin (**146**) and 2\({}^{\prime}\),3\({}^{\prime}\)-dihydroxybavachinin (**147**), which were obtained at the yields of 18% and 7%, respectively, after five days of biotransformation. Biotransformation of bavachinin (**144**) by using _C. blakesleeana_ AS 3.0910 cultures resulted in the formation of three products: (2R,2S)-bavachin 7-O-\(\beta\)-D-glucopyranoside e primers (**148**), (2S)-4\({}^{\prime}\)-hydroxybavachin (**149**) and (2S)-5\({}^{\prime}\)-hydroxybavachin (**150**), which were isolated in the yields of 26%, 2%, and 5%, after five days of biotransformation. In addition, _C. blakesleeana_ AS 3.0910 transformed isobavachalcone (**145**) to isobavachalcone 4-O-\(\beta\)-D-glucopyranoside (**151**), which was obtained in 23% yields, after 5 days of biotransformation [80]. 6-Methylflavone (**152**) was transformed in the broth of entomopathogenic fungus _Isaria fumosorsea_ KCH J2 to 6-methylflavone 8-O-\(\beta\)-D-(4\({}^{\prime}\)-O-methyl)-glucopyranoside (**153**) and 6-methylflavone 4\({}^{\prime}\)-O-\(\beta\)-D-(4\({}^{\prime\prime}\)-O-methyl)-glucopyranoside (**154**), which were obtained in 60.5% and 39.5% yields, respectively, after 7 days of biotransformation [81]. _Isaria_ filamentous fungi are often used as effective biocatalysts for the transformation of flavonoids. Flavone (**97**) was metabolized by _I. fumosorosea_ KCH J2 in 5 days to produce flavone 2\({}^{\prime}\)-O-\(\beta\)-D-(4\({}^{\prime\prime}\)-O-methyl)-glucopyranoside (**155**), flavone 4\({}^{\prime}\)-O-\(\beta\)-D-(4\({}^{\prime\prime}\)-O-methyl)-glucopyranoside (**156**) and 3\({}^{\prime}\)-hydroxyflavone 4\({}^{\prime}\)-O-\(\beta\)-D-(4\({}^{\prime\prime}\)-O-methyl)-glucopyranoside (**157**) with the yields of 5.5%, 14% and 4%, respectively. Compound **156** was also obtained when using _Isaria farinosa_ J1.6 as biocatalyst. Besides, 5-hydroxyflavone (**158**) was converted into 5-hydroxyflavone 4\({}^{\prime}\)-O-\(\beta\)-D-(4\({}^{\prime\prime}\)-O-methyl)-glucopyranoside (**159**) with 29% yield after 7 days in the culture of strain KCH J2. Compound **159** was also obtained under the biocatalysis of _I. farinosa_ J1.4.