# Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review
## 5 Conclusions  
Flavonoids and isoflavuroids have attracted considerable attention due to their low toxicity and remarkable biological activity. Flavonoid and isoflavue pathways are considered the most characteristic natural product pathways in plants. However, microbial sources of isoflavues and flavonoids have received little attention. This is the first review of the fungal and actinomycete sources of isoflavues and flavonoids. Only 24 new compounds of isoflavues and flavonoids from fungi and actinomycetes have been identified; however, some of these are highly potent bioactive compounds that might be potential drug candidates. Compounds **61** and **58** from _Acanthostigmella_ sp. CL12082 demonstrated potent antifungal activity. Compound **61** displayed strong antifungal activity against _C. albicans_ and _A. fumigatus_, with IC\({}_{50}\) values of 0.11 and 0.54 ug/mL, respectively. Similarly, compound **58** displayed extremely strong activity against the fungi, _C. albicans_ and _A. fumigatus_, with IC\({}_{50}\) values of 0.035 and 0.10 ug/mL, respectively [54]. Compound **76** from _Streptomyces_ sp. (strain G246) showed broad-spectrum antimicrobial activity, and its antimicrobial activity was far superior than that of its positive controls, streptomycin and cycloheximide. Compound **76** displayed excellent inhibitory activity against _P. aeruginosa_, _S. enterica_, _E. faecalis_, _S. aureus_, _B. cereus_, and _C. albicans_ with IC\({}_{50}\) values of 16, 32, 8, 1, 4, and 8 ug/mL, respectively [60]. The new compounds **77-79**, derived from marine _Streptomyces_ sp. G248, also demonstrated significant broad-spectrum antimicrobial activity against six pathogens, with IC\({}_{50}\) values in the range of 1-16 ug/mL, and their activities were much higher than those of the positive controls, streptomycin and cycloheximide [61]. To ascertain the therapeutic potential of these compounds, particularly of lavandulylated and halogen atom-bearing flavonoids, further pharmacological, chemical, and toxicological studies are required. Nearly all the isoflavues and flavones from actinomycetes are reported to be produced by _Streptomyces_ sp. ; however, two studies have reported the isolation of isoflavues and flavones from actinomycetes, _M. aurantiaca_ 110B and _Amyclatopsis_ sp. [33,43]. The culture medium of _M. aurantiaca_ 110B for producing compounds **20**, **21**, and **71** was investigated, and the results indicated that the compounds could be detected in the culture medium only when soybean cake is added to the medium. The results also indicated that _M. aurantiaca_ 110B could transform plant daidzein into fucosylated derivatives. Notably, the fermentation medium in which _Amyclatopsis_ sp. produces isoflavues also comprises of soybean meal. Whether these two strains have similar transformation pathways to produce isoflavuoid glycosides requires further investigation. Because of the low bioavailability of isoflavues and flavonoids, the bioconversion of isoflavues and flavonoids has gradually gained research attention [80]. In this review, we summarised the biotransformation of isoflavues and flavonoids by fungi and actinomycetes. Understanding the biotransformation process helps us elucidate not only the metabolic pathways of these compounds but also their mechanisms of action, toxicity, and pharmacological activity [112, 113, 114]. _A. niger_ and _Streptomyces_ sp. are the most adaptable fungi and actinomycetes, respectively, and are the most commonly used biotransformation strains because of their ability to use various isoflavues and flavonoids as substrates for biosynthesis and biotransformation. They usually undergo hydroxylation, methylation, glycosylation, cyclisation, halogenation, and double bond reduction to produce isoflavand flavonoids, which are more beneficial to human health; for instance, methylation enhances substrate stability, hydroxylation enhances antioxidant activity, and glycosylation enhances water solubility.