Microbial biotransformation of water-insoluble herbimycin A to 11-hydroxy-(11-demethoxy)-herbimycin C by Eupenicillium sp. SD017

Herbimycin A, a typically water-insoluble anti-tumor drug and an analog of geldanamycin, was transformed by fungus Eupenicillium sp. SD017. The water solubility and anti-tumor activity of converted products were evaluated after separation, purification, and structure elucidation. The results showed that herbimycin A can be converted into herbimycin C 1 and 11-hydroxy-(11-demethoxy)-herbimycin C 2 with water solubility increased. The latter is a novel compound, and its IC50 to A549, MCF-7, Ehrlich and HeLa cells is 152.9, 0.46, 10.7 and 109.3 μg/ml, respectively, which are nearly in the range of those between herbimycin A and herbimycin C. It is suggested that an O-demethylase or/and methyltransferase may play an important role on biotransformation in this case. This study will firstly serve as a fundamental methodology for further structural alteration and functional improvement of the water-insoluble anti-tumor drugs using microbial resources.