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. 2024 Feb 24;23(1):65.
doi: 10.1186/s12934-024-02338-9.

Multienzymatic biotransformation of flavokawain B by entomopathogenic filamentous fungi: structural modifications and pharmacological predictions

Paweł Chlipała  1 , Tomasz Tronina  2 , Monika Dymarska  2 , Monika Urbaniak  3 , Ewa Kozłowska  2 , Łukasz Stępień  3 , Edyta Kostrzewa-Susłow  2 , Tomasz Janeczko  4
Affiliations

Multienzymatic biotransformation of flavokawain B by entomopathogenic filamentous fungi: structural modifications and pharmacological predictions

Paweł Chlipała et al. Microb Cell Fact. .

Abstract

Background: Flavokawain B is one of the naturally occurring chalcones in the kava plant (Piper methysticum). It exhibits anticancer, anti-inflammatory and antimalarial properties. Due to its therapeutic potential, flavokawain B holds promise for the treatment of many diseases. However, due to its poor bioavailability and low aqueous solubility, its application remains limited. The attachment of a sugar unit impacts the stability and solubility of flavonoids and often determines their bioavailability and bioactivity. Biotransformation is an environmentally friendly way to improve the properties of compounds, for example, to increase their hydrophilicity and thus affect their bioavailability. Recent studies proved that entomopathogenic filamentous fungi from the genera Isaria and Beauveria can perform O-methylglycosylation of hydroxyflavonoids or O-demethylation and hydroxylation of selected chalcones and flavones.

Results: In the present study, we examined the ability of entomopathogenic filamentous fungal strains of Beauveria bassiana, Beauveria caledonica, Isaria farinosa, Isaria fumosorosea, and Isaria tenuipes to transform flavokawain B into its glycosylated derivatives. The main process occurring during the reaction is O-demethylation and/or hydroxylation followed by 4-O-methylglycosylation. The substrate used was characterized by low susceptibility to transformations compared to our previously described transformations of flavones and chalcones in the cultures of the tested strains. However, in the culture of the B. bassiana KCh J1.5 and BBT, Metarhizium robertsii MU4, and I. tenuipes MU35, the expected methylglycosides were obtained with high yields. Cheminformatic analyses indicated altered physicochemical and pharmacokinetic properties in the derivatives compared to flavokawain B. Pharmacological predictions suggested potential anticarcinogenic activity, caspase 3 stimulation, and antileishmanial effects.

Conclusions: In summary, the study provided valuable insights into the enzymatic transformations of flavokawain B by entomopathogenic filamentous fungi, elucidating the structural modifications and predicting potential pharmacological activities of the obtained derivatives. The findings contribute to the understanding of the biocatalytic capabilities of these microbial cultures and the potential therapeutic applications of the modified flavokawain B derivatives.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Biotransformation of flavokawain B (FB1) by M. robertsii MU4 strain
Fig. 2
Fig. 2
Biotransformation of flavokawain B (FB1) by I. tenuipes MU35 strain
Fig. 3
Fig. 3
Biotransformation of flavokawain B (FB1) by B. bassiana KCh J1 strain
Fig. 4
Fig. 4
Biotransformation of flavokawain B (FB1) by B. bassiana BBT and KCh J1.5 strains
Fig. 5
Fig. 5
Biotransformation of flavokawain B (FB1) by B. caledonica KCh J3.3
Fig. 6
Fig. 6
Flavokawain B synthesis
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