SAM- and cobalamin- dependent conversion of estrogens into androgens

细菌降解内分泌干扰和致癌雌激素是从环境中消除是必不可少的。在雌激素降解厌氧细菌中，17 -雌二醇的A环最初以SAM和单电子供体依赖的方式被甲基化成1-脱氢睾酮。该反应被认为是由四个EmtABCD亚基组成的非正统SAM/钴胺依赖性甲基转移酶催化的。在雌激素降解和反硝化过程中，雌脱硝体细胞强烈上调c1代谢，将c1池引导至启动雌激素甲基化的途径。在目前的项目中，我们的目标是(i)分离和生化，动力学和结构表征SAM/ b12依赖的甲基转移酶系统，将雌激素转化为雄激素；（ii）使用由合作伙伴在FOR内提供的SAM-类似物，通过生物正交方法生成新型雄激素类固醇；（iii）建立一个基于D. oestradiolicus的全细胞系统，用于引导c1代谢以实现SAM再生。

The bacterial degradation of endocrine disrupting and carcinogenic estrogens is essential for their elimination from the environment. In estrogen-degrading anaerobic bacteria, ring A of 17beta-estradiol is initially dearomatized by methylation to 1-dehydrotestosterone in a SAM- and one-electron-donor dependent manner. The reaction is supposed to be catalyzed by an unorthodox SAM/cobalamin-dependent methyltransferase composed of the four EmtABCD subunits. During estrogen degradation coupled to denitrification, Denitratisoma oestradiolicus cells strongly upregulate C1-metabolism to channel the C1-pool towards the pathway-initiating methylation of estrogens. In the current project, we aim (i) at isolating and biochemically, kinetically, and structurally characterizing the SAM/B12-dependent methyltransferase system that converts estrogens to androgens, (ii) to use SAM- analogues provided by collaborations partners within the FOR for the generation of novel androgen steroids in bioorthogonal approaches, (iii) to establish a D. oestradiolicus based whole-cell system for channelling C1-metabolism towards SAM-regeneration.