# 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  
In order to obtain \(O\)-dihydroxysoflavones, _Aspergillus saitoi_ was used for transforming daidzein (**1**) and genistin (**33**) to generate 8-hydroxydaidzein (**7**) and 8-hydroxygenistein (**17**), respectively, by deglycosylation and hydroxylation [65]. Three isoflavenes were used to study the biotransformation by _Aspergillus niger_, and it was found that daidzein (**1**) was not metabolized. The C-6 position of 7,4'-dimethoxyisoflavone (**83**) was hydroxylated to form 6-hydroxy-7,4'-dimethoxyisoflavone (**85**), which was then converted into **1** by demethylation of C-7 and C-4' positions. In addition, 7,4'-diacetoxyisoflavone (**84**) was converted into **1** through the hydrolysis of C-7 and C-4' positions [66]. 6,7,4'-Trimethoxyisoflavone (**86**) and 5,7,4'-trimethoxyisoflavone (**87**) were studied for their biotransformation by _A. niger_. They could be converted to 4'-hydroxy-6,7-dimethoxyisoflavone (**8**) and 4'-hydroxy-5,7- dimethoxyisoflavone (**88**), respectively, by demethylation at C-4' position [67]. The isoflavone, luteone [5,7,2',4'-tetrahydro-6-(3,3-dimethylallyl) isoflave] (**38**) could be transformed into 2\",3\"-dihydro-3\"-hydroxyluteone (**89**), 2\",3\"-dihydrohydroxyluteone (**90**), dihydrofuranoisoflavone (**41**) and dihydropyranoisoflavone (**91**) by cultures of _A. flavus_ and _B. cinerea_. The main products **41** and **89** were less toxic to _C. herbarum_ than compound **38**[44]. Two isoflaves, 7-\(O\)-methyl-2,3-dehydrokievittone epoxide (**93**) and 7-\(O\)-methyl-2,3-dehydrokievittone glycol (**94**), were formed from 2,3-dehydrokievittone (**92**) by methylating with ethereal diazomethane under the metabolism by _B. cinerea_. The epoxide was regarded as the key metabolic intermediate involved in the transformation from precursor compounds containing a prenyl side-chain with ortho-hydroxylation to 2,3-dihydroxy-3-methylbutyl-substituted isoflaves [68]. Biotransformation of two flavonoids was studied by using four strains of _A. niger_, three of which were mutated by ultraviolet irradiation. Flavanone (**95**) and 6-hydroxyflavanone (**96**) were transformed to flavan-4-ol (**99**) and 6-hydroxyflavan-4-ol (**101**), respectively, through decarbonylation, and the dehydrogenation at C-2 and C-3 positions produced flavone (**97**) and 6-hydroxyflavone (**102**), respectively. Compound **95** was reduced at C-4 and hydroxylated at C-7 to form 7-hydroxyflavan-4-ol (**100**), and dehydrogenation at C-2 and C-3, along with hydroxylation at C-3 to from 3-hydroxyflavone (**98**) [69]. 2\",3\"-Dihydro-3\"-hydroxywighteone (**106**) was obtained by biotransformation from the antifungal compound, wighteone [5,7,4'-trihydroxy-6-(3,3-dimethylallyl) isoflave] (**103**) under the modification of _A. flavus_ and _B. cinerea_ and the latter was further transformed into dihydrofurano-isoflavone (**104**). Small amounts of dihydropyrano-isoflavone (**105**), dihydrofurano-isoflavone (**104**), and 2\",3\"-dihydrodihydroxywighteone (**107**) were obtained in _A. flavus_ culture medium. Compounds **105** and **107** were obtained in _B. cinerea_ medium [70]. Figure 7: \(Cont\). Figure 7: _Cont._  
Figure 7: Biotransformation of isoflavenes and flavonoids **83–251** by fungi. The study on the biotransformation of filamentous fungi found that _Trichoderma harzianum_ NJ01 could convert Puerarin (**108**) to 3'-hydroxypuerarin (**109**) with a conversion rate of up to 41% under the optimal conditions. In the DPPH free radical scavenging system, compound **109** was 20 times more active than **108**. The solubility of **109** is 1.3 times higher than **108**[71]. Glabratephrin (**110**) was obtained from _Tephrosia purpurea_ and transformed into pseudosemiglabrin (**111**) by the culture of  
Figure 8: Biotransformation of isoflav and flavonoids **252–284** by actinomycetes. _A. niger_. The transformation process is realized by using the open loop and the closed loop of the five-member ring [72]. Flavanone (**95**) is converted by _A.