Biocatalytic and chemical derivatization of the fungal meroditerpenoid chevalone E

Fungal meroditerpenoids include diverse molecules with structural complexity and a broad range of biological activities. We have previously obtained the meroditerpenoid chevalone E (1) and its oxidized analogues by heterologously expressing a cryptic gene cluster found in the fungus Aspergillus versicolor. In this study, we further derivatized 1 into eight chevalone analogues using a single dehydrogenase involved in another meroterpenoid pathway. Some of the new analogues harbor the characteristic hemiacetal bridge, which can be transformed into the spirolactone moiety by simple chemical synthesis. Furthermore, some of the new chevalone analogues exhibit the synergetic inhibition of MDA-MB-231 breast cancer cell viability when combined with the chemotherapeutic agent doxorubicin.

Automated summary

In this study, using a cryptic gene cluster found in the fungus Aspergillus versicolor, researchers successfully synthesized and derived eight new analogues of fungal meroditerpenoids. Some of these analogues exhibited synergistic inhibition of MDA-MB-231 breast cancer cell viability when combined with the chemotherapeutic agent doxorubicin. This study expands our understanding of fungal meroditerpenoids and provides new candidate substances for further research on their biological activities and pharmacological effects.