Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1128/mBio.01259-20
Licence creative commons licence
Title (Primary) Channeling C1 metabolism toward S-adenosylmethionine-dependent conversion of estrogens to androgens in estrogen-degrading bacteria
Author Jacoby, C.; Krull, J.; Andexer, J.; Jehmlich, N. ORCID logo ; von Bergen, M.; Brüls, T.; Boll, M.
Source Titel mBio
Year 2020
Department MOLSYB
Volume 11
Issue 4
Page From e01259-20
Language englisch
Keywords C1 metabolism; S-adenosylmethionine; bioremediation; estrogen; methyltransferase; vitamin B12
Abstract Bacterial degradation of endocrine disrupting and carcinogenic estrogens is essential for their elimination from the environment. Recent studies of the denitrifying, estrogen-degrading Denitratisoma strain DHT3 revealed the conversion of estrogens to androgens by a putative cobalamin-dependent methyltransferase encoded by the emtABCD genes. The methyl donor and its continuous regeneration to initiate estradiol catabolism have remained unknown. Here, large-scale cultivation of the denitrifying bacterium Denitratisoma oestradiolicum with estrogen provided the biomass required for quantitative biochemical analyses. Soluble fractions of extracts from estradiol-grown cells catalyzed the S-adenosyl-l-methionine (SAM)- and Ti(III)-citrate-dependent conversion of 17β-estradiol/estrone to the respective androgens at 0.15 nmol min−1 mg−1. Kinetic studies of 17β-estradiol methylation and reverse 1-dehydrotestosterone demethylation reactions indicated that the exergonic methyl transfer from SAM to the putative cobalamin drives the endergonic methyl transfer from the methylcobalamin intermediate to the phenolic ring A. Based on a high-quality circular genome from D. oestradiolicum, proteogenomic analyses identified a 17β-estradiol-induced gene cluster comprising emtABCD genes together with genes involved in SAM regeneration via l-serine and l-methionine. Consistent with this finding, l-methionine/ATP or l-serine/ATP/tetrahydrofolate/l-homocysteine substituted for SAM as methyl donors, further confirmed by the incorporation of the 13C-methyl-group from 13C-l-methonine into methyl(III)cobalamine and the estrone methylation product androsta-1,4-diene-3-one. This work demonstrates that during bacterial estrogen catabolism, the C1 pool is channeled toward the initiating methyl transfer to ring A. The effective cellular SAM regeneration system may serve as a model for whole-cell SAM-dependent methylation reactions of biotechnological interest.
Persistent UFZ Identifier
Jacoby, C., Krull, J., Andexer, J., Jehmlich, N., von Bergen, M., Brüls, T., Boll, M. (2020):
Channeling C1 metabolism toward S-adenosylmethionine-dependent conversion of estrogens to androgens in estrogen-degrading bacteria
mBio 11 (4), e01259-20 10.1128/mBio.01259-20