Romano Diego, Ferrario Valerio, Mora Diego, Lenna Roberto, Molinari Francesco
Dipartimento di Scienze e Tecnologie Alimentari e Microbiologiche, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy.
Steroids. 2008 Jan;73(1):112-5. doi: 10.1016/j.steroids.2007.09.008. Epub 2007 Oct 2.
The enantioselective reduction of tibolone into the corresponding 3alpha-hydroxy or 3beta-hydroxy metabolite can be controlled by choosing suited strains of yeasts and biotransformation conditions. A restricted screening performed among 52 yeasts showed that the 3alpha-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 3beta-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 3beta/3alpha with complete molar conversion within 72h when the initial concentration of substrate was below 2.5g/L. K. lactis CBS 2359 gave a 99:1 ratio of 3alpha/3beta with complete conversion in 64h.
通过选择合适的酵母菌株和生物转化条件，可以控制替勃龙对映选择性还原为相应的3α-羟基或3β-羟基代谢物。在52种酵母中进行的有限筛选表明，使用各种菌株（如乳酸克鲁维酵母CBS 2359）可优先获得具有高差向异构纯度的3α-差向异构体，而只有酿酒酵母CBS 3093以3β-差向异构体作为主要产物。对乳酸克鲁维酵母CBS 2359和酿酒酵母CBS 3093还原替勃龙的过程进行了优化。当底物初始浓度低于2.5g/L时，酿酒酵母CBS 3093在72小时内以96:4的3β/3α比例实现了完全摩尔转化。乳酸克鲁维酵母CBS 2359在64小时内以99:1的3α/3β比例实现了完全转化。
