Enantioselective production of 3-hydroxy metabolites of tibolone by yeast reduction

The enantioselective reduction of tibolone into the corresponding 3α-hydroxy or 3β-hydroxy metabolite can be controlled by choosing suited strains of yeasts and biotransformation conditions. A restricted screening performed among 52 yeasts showed that the 3α-epimer was preferentially obtained with high epimeric purity with various strains (i.e. with Kluyveromyces lactis CBS 2359), while only Saccharomyces cerevisiae CBS 3093 gave the 3β-epimer as major product. The reduction of tibolone with K. lactis CBS 2359 and S. cerevisiae CBS 3093 was optimised. S. cerevisiae CBS 3093 furnished a 96:4 ratio of 3β/3α with complete molar conversion within 72 h when the initial concentration of substrate was below 2.5 g/L. K. lactis CBS 2359 gave a 99:1 ratio of 3α/3β with complete conversion in 64 h.