Microbial Transformations of Two Beyerane-Type Diterpenes by Cunninghamella echinulata

Microbial transformations
of two tetracyclic beyerane-type diterpenes, ent-16β-oxobeyeran-19-oic
acid (1) and
its chemical reduction product, ent-16β-hydroxybeyeran-19-oic
acid (2), by the filamentous fungus Cunninghamella
echinulata ATCC 8688a yielded eight metabolites (3–10). Incubation of the substrate 2 with C. echinulata afforded three new hydroxylated ones
(3–5) along with two known ones (6–7), while incubation of 1 gave
three known ones (8–10). The new compounds were
characterized by 1D and 2D NMR as well as HRESIMS analysis, and the
stereostructures of 3 and 4 were confirmed
by X-ray crystallography. The bioreactions were involved not only
in stereoselective incorporation of hydroxyl groups at inert positions
C-7, -9, -12, and -14 of the two beyerane diterpenes but also in glucosidation
at C-19 of 2. This is the first report on the biotransformation
of the diterpenes by using C. echinulata. All compounds were assayed for their α-glucosidase inhibitory,
neurotrophic, anti-inflammatory, and phytotoxic activity, and only
in neurotrophic assay compounds, 2 and 9 were found to display nerve growth factor-mediated neurite-outgrowth
promoting effects in PC12 cells; the others were inactive.