# 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  
5,7,4'-Thirhydroxyisoflavon (**2**) is present in soybean meal. Fermentation media containing soybean meal could be used to isolate two new isoflavonoids, 8-chlorogenistein (**19**) and 6,8-dichlorogenicin (**252**), from _Streptomyces griseus_. However, the strain could not produce compounds **19** and **252** without soybean meal, and this suggests that the strain could biotransformation compound **2** into chlorinated metabolites **19** and **252**. These new isoflavonoids were produced through microbial halogenation. When _S. griseus_ was cultivated with radiologically labelled acetate or phenylalanine, no labelled isoflavones were obtained. The result illustrated that isoflavonoids isolated from streptomycetes may have originated from the medium containing plant-derived nutrient components rather than having a microbial biosynthetic origin [63]. A shuffled biphenyl dioxygenase holoenzyme with broad substrate specificity was coded by the bphA1(2072)A2A3A4 gene cluster, and the gene cluster was introduced into _Streptomyces lividans_. The recombinant _S. lividans_ cell could transform flavone (**97**) and flavanone (**95**) into 3'-hydroxyflavone (**214**), 2',3'-dihydroxyflavone (**253**), 2',3'-dihydroxyflavanone (**254**), 3'-hydroxyflavanone (**255**), and 2'-hydroxyflavanone (**256**). In addition, 6-hydroxyflavone (**102**) and 6-hydroxyflavanone (**96**) were transformed into 3',6-dihydroxyflavone (**257**) and 2',6-dihydroxyflavanone (**258**), respectively. Among all the biotransformed compounds, only compounds **253** and **254** exhibited free radical scavenging activity [89]. Two prenyltransferases, NphB and SCO7190, obtained from two _Streptomyces_ sp., namely CL190 and _S. coelicolor_ A3(2), respectively, could synthesize various prenylated compounds from aromatic substrates, including flavonoids. The recombinant NphB and SCO7190 were overproduced in _E. coli_ and purified to homogeneity. Results of the recombinant NphB catalysis are as follows: 7-O-Geranyl naringenin (**259**) and 6-geranyl naringenin (**260**) were synthetized from naringenin (**116**) and geranyl diphosphate (GPP); 7-O-geranyl apigenin (**261**) and 6-geranyl apigenin (**262**) were synthetized from apigenin (**135**) and GPP; 7-O-geranyl genistein (**263**) was synthetized from genistein (**2**) and GPP; 7-O-geranyl daidzein (**264**) and 8-geranyl daidzein (**265**) were synthetized from daidzein (**1**) and GPP. The result of the recombinant SCO7190 catalysis showed that 6-dimethyllallyl naringenin (**266**) was synthetized from naringenin and DMAPP [90]. NphB, a propenyl transferase, can maintain regioselectivity for propenyl transfer in some cases. A marine-derived _Streptomyces_ sp. 060524 was able to hydrolyze the glycosidic bond of isoflav glycosides. Genistein glycosides (**33**) and diadzein glycosides (**34**) were converted to genistein (**2**) and diadzein (**1**) by \(\beta\)-glucosidase, respectively. With the catalyzation by hydroxylase, the strain selectively hydroxylated at the 3\({}^{\prime}\)-position and transformed compounds **1** and **2** into 3\({}^{\prime}\)-hydroxygenistein (**16**) and 3\({}^{\prime}\)-hydroxydaidzein (**9**), respectively. In addition, glycitein glycoside (**37**) was also converted to glycitein (**267**) by \(\beta\)-glucosidase. Compounds **2** and **16** possessed excellent cytotoxicity against K562 human chronic leukemia [91]. A series of flavonoids incubating with the strain _Streptomyces_ sp. M52104 could obtain transformational metabolites. Quercetin (**63**) was converted into quercetin-4\({}^{\prime}\)-O-\(\beta\)-D-glucuronide (**269**), quercetin-7-O-\(\beta\)-D-glucuronide (**270**), quercetin-3-O-\(\beta\)-D-glucuronide (**271**), and quercetin-3\({}^{\prime}\)-O-\(\beta\)-D-glucuronide (**272**) for 65 h of incubation.