Biotransformation of labdane and halimane diterpenoids by two filamentous fungi strains

Abstract

Biotransformation of natural products by filamentous fungi is a powerful and effective approach to achieve derivatives with valuable new chemical and biological properties. Although diterpenoid substrates usually exhibit good susceptibility towards fungi enzymes, there have been no studies concerning the microbiological transformation of halimane-type diterpenoids up to now. In this work, we investigated the capability of <i>Fusarium oxysporum</i> (a fungus isolated from the rhizosphere of <i>Senna spectabilis</i>) and <i>Myrothecium verrucaria</i> (an endophyte) to transform halimane (<b>1</b>) and labdane (<b>2</b>) acids isolated from <i>Hymenaea stigonocarpa</i> (Fabaceae). Feeding experiments resulted in the production of six derivatives, including hydroxy, oxo, formyl and carboxy analogues. Incubation of <b>1</b> with <i>F. oxysporum</i> afforded 2-oxo-derivative (<b>3</b>), while bioconversion with <i>M. verrucaria</i> provided 18,19-dihydroxy (<b>4</b>), 18-formyl (<b>5</b>) and 18-carboxy (<b>6</b>) bioproducts. Transformation of substrate <b>2</b> mediated by <i>F. oxysporum</i> produced a 7<i>α</i>-hydroxy (<b>7</b>) derivative, while <i>M. verrucaria</i> yielded 7<i>α</i>- (<b>7</b>) and 3<i>β</i>-hydroxy (<b>8</b>) metabolites. Unlike <i>F. oxysporum</i>, which showed a preference to transform ring B, <i>M. verrucaria</i> exhibited the ability to hydroxylate both rings A and B from substrate <b>2</b>. Additionally, compounds <b>1</b>-<b>8</b> were evaluated for inhibitory activity against Hr-AChE and Hu-BChE enzymes through ICER-IT-MS/MS assay.