Retroconversion of estrogens into androgens by bacteriaviaa cobalamin-mediated methylation

Abstract

AbstractSteroid estrogens modulate physiology and development of vertebrates. Biosynthesis of C18estrogens from C19androgens by the O2-dependent aromatase is thought to be irreversible. Here, we report a denitrifyingDenitratisomasp. strain DHT3 capable of catabolizing estrogens or androgens anaerobically. Strain DHT3 genome contains a polycistronic gene clusteremtABCDdifferentially transcribed under estrogen-fed conditions.emtABCDencodes a cobalamin-dependent methyltransferase system conserved among estrogen-utilizing anaerobes;emtA-disrupted strain DHT3 can catabolize androgens but not estrogens. These data, along with the observed androgen production in estrogen-fed strain DHT3 cultures, indicate the occurrence of a cobalamin-mediated estrogen methylation to form androgens. Consistently, the estrogen conversion into androgens in strain DHT3 cell-extracts requires methylcobalamin and is inhibited by propyl-iodide, a specific inhibitor of cobalamin-dependent enzymes. The identification of the cobalamin-mediated estrogen methylation thus represents an unprecedented metabolic link between cobalamin and steroid metabolism and suggests that retroconversion of estrogens into androgens occurs in the biosphere.