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.
biocatalysis, hydroxylation, biotransformation, Cunninghamella echinulata, beyerane diterpenes
NCBI PubMed ID: 32216259Publication DOI: 10.1021/acs.jafc.0c00592Journal NLM ID: 0374755Publisher: American Chemical Society
Correspondence: Gao JM
Institutions: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, China
Methods: 13C NMR, 1H NMR, IR, X-ray, inhibition studies, TLC, ESI-MS, extraction, optical rotation measurement, CC, cell growth, HR-ESI-MS, enzymatic assay, determination of NO production, cell viability assay, sonication, phytotoxicity assay
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