A novel biotransformation process of 4′-demethylepipodophyllotoxin to 4′-demethylepipodophyllic acid by Bacillus fusiformis CICC 20463

The novel biotransformation process of 4′-demethylepipodophyllotoxin to produce 4′-demethylepipodophyllic acid was developed for the first time. Based on the capability of modifying 4′-demethylepipodophyllotoxin structure, Bacillus fusiformis CICC 20463, Bacillus subtilis CCTCC AB93174, Pseudomonas aeruginosa CCTCC AB93066 and Pseudomonas oleovorans CGMCC 1.1641 were screened out from the eight tested strains. Among them, B. fusiformis was selected for the following study because of its high substrate conversion. The biotransformation product was separated from the biotransformation broth by macroporous resin D312, and identified as 4′-demethylepipodophyllic acid by the comparison analysis of 1H NMR, 13C NMR, and ESI-MS spectrums with those of 4′-demethylepipodophyllotoxin. This suggests that B. fusiformis, P. aeruginosa, B. subtilis and P. oleovorans had the ability to transform 4′-demethylepipodophyllotoxin into 4′-demethylepipodophyllic acid. The established biotransformation process will give reference to the biotransformation study of other bioactive natural leading compounds.