# Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review
## 3 Microbiological Transformation of Isoflavonoids and Flavonoids
### Biotransformation of Isoflavones and Flavonoids in Actinomycetes
Furthermore, rutin (**268**) was only transformed into compounds **269-271** by incubating 90 h. Both 25-naringenin (**273**) and 25-naringenin-7-O-\(\beta\)-D-glucopyranoside (**274**) were able to convert into naringenin-7-O-\(\beta\)-D-glucuronide (**275**) and naringenin-4\({}^{\prime}\)-O-\(\beta\)-D-glucuronide (**276**) by incubating 65 h [92]. Quercetin (**63**) incubating with _Streptomyces rimosus_ subsp. _rimosus_ ATCC 10970 was able to be transformed into quercetin-7-O-\(\beta\)-4\({}^{\prime\prime}\)-deoxy-hex-4\({}^{\prime\prime}\)-enopyranosiduronic acid (**277**) in 72 h [93]. Biottransformation of genistein (**2**) in the culture of _Streptomyces_ sp. MBT76 obtained 4\({}^{\prime}\),7-di-hydroxy-5-methoxy-isoflavone (**278**), 4\({}^{\prime}\)-hydroxy-5,7-dimethoxy-isoflavone (**88**), 4\({}^{\prime}\)-hydroxy-5,7,8-trimethoxy-isoflavone (**279**), and 7\(A^{\prime}\)-dihydroxy-5,8-dimethoxy-isoflavone (**280**) [22]. However, methylated isoflaves exhibited lower bioactivity than the unmethylated precursors. Two flavanones, pinochemrin (**54**) and naringenin (**116**), two flavones, chrysin and apigenin, together with a flavonoid, kaempfer, were catalyzed by CYP105D7, a cytochrome P450 from _Streptomyces avermitilis_[94]. Through experiments, CYP105D7 enabled the catalysis of the hydroxylation of **54** and **116**. The 3\({}^{\prime}\)-position of **116** was hydroxylated by CYP105D7, while the hydroxylated position of **54** could not be determined. Nonetheless, the retention time detected in HPLC implied that 3-hydroxylation or 4\({}^{\prime}\)-hydroxylation did not occur. A putative \(O\)-methyltransferaseane OMT gene SpOMT7740 was obtained from the sequence information of _Streptomyces peucetius_ ATCC27952. Introducing the gene into _E. coli_, BL21 was used to detect the substrate promiscuity and perform functional characterization. Flavonoids were added into the fermentation broth of _E. coli_ BL21 for biotransformation. The theoretical and experimental results were as follows: genistein (**2**), 3-hydroxyflavone (**98**), luteolin (**194**), 7,8-dihydroxyflavone (**281**), and phloretin (**282**) were successively converted into tri-\(O\)-methoxygenistein, 3-\(O\)-methoxy, mono-\(O\)-methoxyletolin, 7-hydroxy-8-\(O\)-methoxy, and mono-\(O\)-methoxyphloretin [95]. Four known isoflavonoids, diadzein (**1**), genistein (**2**), diadzein-7-\(O\)-\(\alpha\)-L-rhammoside (**23**), and genistein-7-\(O\)-\(\alpha\)-L-rhammoside (**25**), were derived from Indonesian actinomycete _Streptomyces_ sp. TPU1401A [32]. Compounds **1** and **2** were able to transform into the 7-O-glycoside derivatives, **23** and **25**, respectively, by the strain TPU1401A. Compounds **23** and **25** promoted the strain TPU1401A grown better than compounds **1** and **2**. This phenomenon suggested that the strain TPU1401A transformed isoflaves into isoflavvemos to isoflavone glycosides to hasten growth. Studies showed that ring A hydroxyflavones were transformed to the corresponding C-4\({}^{\prime}\) hydroxylated metabolites; the rate and yields of production were related to the distance between the C-4 carbonyl group and the hydroxyl group in the A ring. During the process of biotransformation in the culture of _Streptomyces fulvissimus_, 6-hydroxyflavone (**102**) and 7-hydroxyflavone (**121**) converted into 6,\(A^{\prime}\)-dihydroxy flavone (**119**) and 7,\(A^{\prime}\)-dihydroxyflavone (**122**) with a medium and slow reaction, respectively. 5-Hydroxyflavone (**158**) was completely transformed to 5,\(A^{\prime}\)-dihydroxyflavone (**283**) and 5,3\({}^{\prime}\),\(A^{\prime}\)-dihydroxyflavone (**284**) for two days with a rapid reaction. These results demonstrated that the highest rate of transformation was observed when the hydroxy group was closest to the carbonyl group [96].