Biotransformation of betulinic acid by Circinella muscae and Cunninghamella echinulata to discover anti-inflammatory derivatives

Biotransformation of betulinic acid was carried out with Circinella muscae CGMCC 3.2695 and Cunninghamella echinulata CGMCC 3.970, yielded six previously undescribed hydroxylated metabolites and four known compounds. C. muscae could catalyze the regioselecitve hydroxylation and carbonylation at C-3, C-7, C-15 and C-21 to yield seven products. C. echinulata could catalyze the C-1, C-7 and C-26 regioselecitve hydroxylation and acetylation to yield five metabolites. The structures of the metabolites were established based on extensive NMR and HR-ESI-MS data analyses. Furthermore, most of the metabolites exhibited pronounced inhibitory activities on lipopolysaccharides-induced NO production in RAW264.7 cells.