Biotransformation of diterpenes from Copaifera sp. oleoresins using filamentous fungi

The labdane diterpenes ent-polyalthic (PA) and ent-dihydroagathic (DA) acids are secondary metabolites found in several plants including the trees of Copaifera sp. (Fabaceae-Caesalpinioideae), from which is extracted an active oleoresin rich in diterpenes [1]. Although these oleoresins are widely used in folk medicine [2], little is known about their metabolism. Biotransformation studies are an important approach to understand in vivo transformations of bioactive compounds [3]. The metabolism of two major constituents of Copaifera duckei oleoresin was investigated using filamentous fungi. An amount of 120 mg of PA and 150 mg of DA were incubated with an initial inoculum of 1 × 10⁶ spores/mL of Aspergillus brasiliensis and Cunninghamella echinulata, respectively. The biotransformation processes were carried out in flasks containing Koch's K1 medium, at 30 °C and 120 rpm for five days. After the incubation period, the culture broth was filtered and partitioned with ethyl acetate to obtain the crude extracts (161 mg and 244 mg of PA and DA biotransformation's extracts, respectively). The biotransformation metabolites were isolated by chromatographic procedures and identified using UHPLC-ESI-MS with Orbitrap mass analyzer and NMR. Both fungi promoted hydroxylation reactions in different positions of the labdane nucleus. These results can contribute to the understanding of the metabolism of Copaifera sp. medicinal oleoresins.

Capes, FAPESP (grants 2016/25201 – 7 and 2011/13630 – 7) and CNPq.

[1] Borges CHG. et al. Chem Biodivers 2016; 13: 1348 – 1356.

[2] Leandro LM. et al. Molecules 2012; 17: 3866 – 3889.

[3] Paludo CR. et al. Eur J Drug Metab Pharmacokinet 2017;42: 213 – 220.