Retroconversion of estrogens into androgens by bacteria via a cobalamin-mediated methylation
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
117
Journal Volume
117
Journal Issue
3
Journal Issue
3
Pages
1395 - 1403
Start Page
1395
End Page
1403
ISSN
00278424
Date Issued
2020-01-21
Author(s)
Abstract
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.
Subjects
Biocatalysis
Cobalamin-dependent methyltransferase
Estrogens
Microbial metabolism
Steroids
Publisher
National Academy of Sciences
Type
journal article