SAM- and cobalamin- dependent conversion of estrogens into androgens

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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.