Epoxidation of ent-pimara-8(14),15-dien-19-oic acid by whole cells of the endophytic fungus Aspergillus sclerotiorum

Abstract

Abstract The diterpene ent -pimara-8(14),15-dien-19-oic acid ( 1 ) was converted into four oxidized diterpenes, 15,16-epoxy- ent -pimar-8(14)-en-19-oic acid ( 1a ), 15,16-epoxy-17-hydrxy- ent -pimar-8(14)-en-19-oic acid ( 1b ), 15,16-dihydroxy- ent -pimar-8(14)-en-19-oic acid ( 1c ), and 15-oxo-16-hydroxy- ent -pimar-8(14)-en-19-oic acid ( 1d ), when added to Aspergillus sclerotiorum cells growing in liquid cultures, being 1b and 1d non described substances. A. sclerotiorum oxidized the double-bound Δ 15 , letting intact the Δ 8(14) , differently from previous studies where another Aspergillus specie oxidized carbons from the tricyclic part of the same substrate 1 . Abietic acid ( 2 ), a diterpene having two endocyclic C-C double-bounds (Δ 7(8) and Δ 13(14) ) was used to challenge this putative regioselectivity. The fungus oxidized one of the methyl groups at C-13 in a similar way shown by diterpene 1 , producing 16-hydroxyabietic acid ( 2a ). The tblastn analyses of whole-genome contigs indicated that A. sclerotiorum contains an enzyme similar to CYP105A1 from Streptomyces griseolus . The ent -pimaric acid ( 1 ) and its derived products 1a - 1d were tested for antiparasitic activities against Leishmania amazonensis and Trypanozoma cruzi .