# 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
niger_ MB and _Penicillium chemresinum_ 113, and two flavonoids, 6-hydroxyflavanone (**96**) and 4-hydroxyflavanone (**114**), were obtained by hydroxylation, and three dihydrohalcones with hydroxyl groups were formed and identified as 2',5'-dihydroxyhydrochalcone (**112**), 2'-hydroxydihydrochalcone (**113**), and 2',4-dihydroxyhydrochalcone (**115**), respectively [21]. Prenylated flavonoids are usually sourced from medicinal plants, and because of restrictions on bioavailability and the high extraction costs, it is essential to study their biological origins. Studies on the biotransformation showed that naringenin 8-dimethylyltransferase expressed by transgenic yeast could convert naringenin (**116**) into 8-dimethylallylInaringenin (**117**). This was an example to provide a method for the production of prenylated flavonoids that rarely occur in nature [73]. Biotransformation by _A. niger_ MB using 6- and 7-methoxyflavones as substrates showed that 6-methoxyflavone (**118**) and 7-methoxyflavone (**120**) were converted to 6-hydroxyflavone (**102**) and 7-hydroxyflavone (**121**) by demethylation at C-6, and then to from 6,4'-dihydroxyoxflavone (**119**) and 7,4'-dihydroxyflavone (**122**) by demethylation at C-6 and hydroxylation at C-4' [74]. The resulting products had a stronger antioxidant activity than the substrates. The biotransformation of 7-hydroxyflavanone (**123**) by three _Aspergillus_ strains (_A. ochracus_ 456, _A. niger_ 13/5) and one _Penicillium_ strain (_P. chemresinum_ 113) were studied. In _P. chemresinum_ 113, compound **123** was converted to 7-methoxyflavanone (**124**) by methylation with a conversion rate of 24%, and to obtain 3',4'-dihydroxy-7-methoxyflavanone (**125**) by methylation combined with hydroxylation at C-3 and C-4 positions, with a conversion rate of 19%. In _A. ochracus_ 456 and _A. niger KB_, the carbonyl group of compound **123** was reduced to form 2,4-_cis_-7-hydroxyflavan_-4-ol (**100**) and compound **125**, respectively, with each conversion yields of 74% and 12%. 2,4-_trans_-5,7-Dihydroxyflavan_-4-ol (**126**) was obtained by _A. ochracus_ transformation using compound **123** as substrate. In _A. niger_ 13/5, substrate **123** was converted to 7-hydroxyflavone (**121**) by dehydrogenation at C-2 and C-3 positions with a conversion rate of up to 98%. Most of the products were found to have more oxidative activity than the substrate [75]. Xanthohumol (**127**) was converted as a substrate to obtain (2)-8-[4''-hydroxy-3''-methyl-(2''-Z)-butenyl]-4',7-dihydroxy-5-methoxy-flavanone (**130**) and (2)-8-[5''-hydroxy-3''-methyl-(2''-E)-butenyl]-4',7-dihydroxy-5-methoxyflavanone (**131**) by _Cunningham chichumulata_ NRRL 3655. Compounds **127**, **130**, (_E_)-2''-(2''-hydroxyisopropyl)-dihydrofurano[2'',3'',4'',3'']-2',4-hydroxy-6'-methoxychalcone (**128**) and (2)-2''-(2''-hydroxyisopropyl)-dihydrofurano[2'',3'',7',8]-4'-hydroxy-5-methoxyflavanone (**129**) were obtained from _Pichia membranifaciens_ which showed antimalarial activity against _Plasmodium falciparum_[76]. Three compounds, apigenin 5-\(O\)-\(\alpha\)-L-hammopyranosyl-(1\(\rightarrow\)3)-\(\beta\)-D-glucopyranoside (**132**), 5-\(O\)-\(\alpha\)-L-hammopyranosyl-(1\(\rightarrow\)2)-(6''-\(O\)-acetyl)-\(\beta\)-D-glucopyranoside (**133**) and chrysoeriol 5-\(O\)-\(\alpha\)-L-hammopyranosyl- (1\(\rightarrow\)4)-(6''-\(O\)-acetyl)-\(\beta\)-D-glucopyranoside (**134**) were obtained from the leaves of _Cephalotaxus haringtonia_, and they were used as substrates for biotransformation by _Paraconiothrium variable_. Compounds **133** and **134** were deglycosylated to form apigenin (**135**), then compound **134** was converted to chrysoeriol (**136**) [77]. Biotransformation was performed using isoflavones and 4'-fluoroisoflavones as substrates by _A. niger_ and _Cunningham elegans_. Both fungi rapidly convert isoflavones into several metabolites. They metabolize isoflavones (40 mg/L) with half-lives of 1.6 and 4.2 days, respectively.