# Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review
## 2 Isoflavonoids and Flavonoids from Actinomycetes and Fungi
### Flavonoids
#### 2.2.1 Simple Flavononoids  
_Trichoderma_ strains are widely used to inhibit pathogens and promote the growth of plants. LC-QQQ-MS showed that three simple flavonoids, dihydromyricetin (**50**), isorhamnetin (**51**), and 4-hydroxy-5,7-dimethoxyylavanone (**52**), existed in the culture broth of fungus _T. asperellum_ TJ01, and their proportion was the highest when cultured at 72 h. [46]. Three flavonoids, named 7-O-methylnaringenin (**53**), pinochemrin (**54**), and (-)-epictechin (**55**), were isolated from the endophytic fungus _Annulolupyoxylon elevidiscus_ BCRC 34014, which was isolated from decorticated woods. It is worth mentioning that this is the first time that flavonoids have been found in this species [47]. The endophytic fungus _Xylaria papulis_ BCRC 09F0222 was isolated from hairy woody plants. Three flavonoids, named myricetin (**50**), myricitrin (**73**), and quercetin (**74**), were obtained from this strain [48]. Since the fungus was cultivated on rice, which is a feeding plant known to produce myricetin and other flavonoids [49], these metabolites might be derived from rice or synthesized by modifying the existing flavonoid precursors in culture medium. Dechlorochlorlavonin (**56**), a known flavonoid derivative, was isolated from the fungus _Aspergillus candidus_ Bdf-2 derived from insects. Compound **56** was assessed for antibacterial activities against _Ralstonia solanacearum_ and _Staphylococcus aureus_ ATCC29213 with MIC values of 64 ug/mL. However, no antioxidant activity was detected [50]. A new flavonoid, named 6,8,5',6'-tetrahydrooxy-3'-methylflavone (**57**), was obtained from the fungal strain _Penicillium_ sp. SCSGAF 0023. This strain could help the host gorgonian corals against marine pathogenic bacteria, biological pollution organisms, and other invaders by producing antifouling and antibacterial compounds. Compound **57** had potent antifouling activity against _Balanus amplititrite_ larvae settlement with an EC\({}_{50}\) value of 6.7 ug/mL [51]. A new antifungal antibiotic, 3'-chloro-2',5-dihydroxy-3,7,8-trimethoxy flavone (**58**) was isolated from _A. candidus_ strains ATCC 20022 and CMI 16046 [52]. Two new flavonoids named aspergillones A (**59**) and B (**60**) were isolated from the fungus _A. candidus_. The strain was isolated from the gorgonian coral _Anthogorgia ochracea_, which was collected from the South China Sea. Compound **60** displayed only weak inhibitory activity against \(\alpha\)-glucosidase with an IC\({}_{50}\) value of 244 ug/mL. Cytotoxicity and antibacterial activity were not showed for compound **59**[53]. In addition, chlorflavonin (**58**), 3'-bromo-2',5-dihydroxy-3,7,8-trimethoxyflavone (**61**), and dechlorochlorlavonin (**62**) were isolated from the fermentation broth of the fungus _Acanthostigmella_ sp. CL12082. Compound **61** showed strong antifungal activity against _Aspergillus fumigatus_ and _Candida albicans_ with IC\({}_{50}\) values of 0.54 and 0.11 ug/mL. Compound **58** displayed significant activity against the growth of pathogenic fungi, _C. albicans_ and _A. fusigatus_ with IC\({}_{50}\) values of 0.035 and 0.10 ug/mL,  
Figure 6: Reported structures of complex flavonoids **67–74** from fungi and actinomycetes. as well as against the growth of HeLa cells IC\({}_{50}\) values of 20 ug/mL. At the same time, these three compounds showed weak inhibition of growth of pathogenic fungi, _Cryptococcus neoformans_ with IC\({}_{50}\) values of 20, 12, and 16 ug/mL, respectively [54]. Quercetin (**63**) was produced by an endophytic fungi _Psathyrella candleana_ from the seed of Ginkgo biloba. It displayed antibacterial activity against \(S\). _aureus_ with MIC values of 0.3906 mg/mL [55]. A study reported the isolation and determination of WS7528 (**64**), produced by _Streptomyces_ sp. No. 7528 derived from a soil sample obtained at Nara Prefecture, Japan.