Research team at the Biodiversity Research Center, Academia Sinica, found that anaerobic bacteria are able to transform estrogens into androgens through a cobalamin-dependent methylation.
Androgens and oestrogens are steroid hormones used to modulate physiology, development and reproduction in animals. C18 oestrogens are biosynthesized through the removal of the C-19 angular methyl group from C19 androgens, resulting in the formation of an aromatic A-ring. Formation of this aromatic ring occurs through the cleavage of an oxidative bond between steroidal C-10 and C-19, catalysed by an aromatase. Reversal of this process proved to be thermodynamically challenging and has not been reported in any organism.
At the Biodiversity Research Center, Academia Sinica, Dr. Chiang Yin-Ru and his research team have been studying anaerobic steroid metabolism in bacteria for the past decade. Their previous study published in Frontiers in Microbiology indicated that anaerobic bacteria are able to transform androgens into oestrogens through oxygenase-independent pathway. Recently, they found that anaerobic bacteria are able to transform oestrogens into androgens through a cobalamin-dependent methylation.
Corresponding genes were also identified and proposed biochemical mechanisms involved in the retro-conversion of oestrogens to androgens. The discovery of the cobalamin-dependent oestrogen methylation reaction thus represents an unprecedented metabolic link between cobalamin and steroid metabolism. These results were published on 21 January 2020 on Proceedings of the National Academy of Sciences (PNAS).
Initially, steroid hormones were thought to be exclusively produced by animals and thus used as biomarkers specific to eukaryotes. Dr. Chiang and his team demonstrated for the first time that conversion of oestrogen to androgen occurs readily in the anaerobic biosphere.
Many studies have shown that gut microbiota affects the sex steroid hormone profile in the host. However, mechanism of action and key bacterial components are yet to be discovered. Dr. Chiang and his research team are attempting to isolate and characterize the gut anaerobes capable of interconversion of sex steroid hormones. In the future, these sex steroids-transforming anaerobes isolated from human gut may be used as probiotics to facilitate the homeostasis of sex hormones in human beings. [APBN]