Retroconversion of estrogens into androgens by bacteria via a cobalamin-mediated methylation

Po Hsiang Wang, Yi Lung Chen, Sean Ting Shyang Wei, Kan Wu, Tzong Huei Lee, Tien Yu Wu, Yin Ru Chiang

研究成果: 雜誌貢獻期刊論文同行評審

28 引文 斯高帕斯(Scopus)


Steroid estrogens modulate physiology and development of vertebrates. Conversion of C19 androgens into C18 estrogens is thought to be an irreversible reaction. Here, we report a denitrifying Denitratisoma sp. strain DHT3 capable of catabolizing estrogens or androgens anaerobically. Strain DHT3 genome contains a polycistronic gene cluster, emtABCD, differentially transcribed under estrogen-fed conditions and predicted to encode a cobalamin-dependent methyltransferase system conserved among estrogen-utilizing anaerobes; an emtA-disrupted DHT3 derivative could catabolize androgens but not estrogens. These data, along with the observed androgen production in estrogen-fed strain DHT3 cultures, suggested the occurrence of a cobalamin-dependent 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-dependent 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.

頁(從 - 到)1395-1403
期刊Proceedings of the National Academy of Sciences of the United States of America
出版狀態已出版 - 21 1月 2020


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