Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria

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-depend...

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Autores principales:	Christian Jacoby, Joris Krull, Jennifer Andexer, Nico Jehmlich, Martin von Bergen, Thomas Brüls, Matthias Boll
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	C1 metabolism S-adenosylmethionine bioremediation estrogen methyltransferase vitamin B12 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/010665a58f0c418c86d0559e4e0ccf02
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spelling	oai:doaj.org-article:010665a58f0c418c86d0559e4e0ccf022021-11-15T15:56:44ZChanneling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria10.1128/mBio.01259-202150-7511https://doaj.org/article/010665a58f0c418c86d0559e4e0ccf022020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01259-20https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Estrogens comprise a group of related hormones occurring in predominantly female vertebrates, with endocrine disrupting and carcinogenic potential. Microbial biodegradation of estrogens is essential for their elimination from surface waters and wastewater. Aerobic bacteria employ oxygenases for the initial cleavage of the aromatic ring A. In contrast, anaerobic degradation of estrogens is initiated by methyl transfer-dependent conversion into androgens involving a putative cobalamin-dependent methyltransferase system. The methyl donor for this unprecedented reaction and its stoichiometric regeneration have remained unknown. With the biomass obtained from large-scale fermentation of an estrogen-degrading denitrifying bacterium, we identified S-adenosyl-methionine (SAM) as the methyl donor for the cobalamin-mediated methyl transfer to estrogens. To continuously supply C1 units to initiate estrogen degradation, genes for SAM regeneration from estradiol-derived catabolites are highly upregulated. Data presented here shed light into biochemical processes involved in the globally important microbial degradation of estrogens.Christian JacobyJoris KrullJennifer AndexerNico JehmlichMartin von BergenThomas BrülsMatthias BollAmerican Society for MicrobiologyarticleC1 metabolismS-adenosylmethioninebioremediationestrogenmethyltransferasevitamin B12MicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	C1 metabolism S-adenosylmethionine bioremediation estrogen methyltransferase vitamin B12 Microbiology QR1-502
spellingShingle	C1 metabolism S-adenosylmethionine bioremediation estrogen methyltransferase vitamin B12 Microbiology QR1-502 Christian Jacoby Joris Krull Jennifer Andexer Nico Jehmlich Martin von Bergen Thomas Brüls Matthias Boll Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria
description	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. IMPORTANCE Estrogens comprise a group of related hormones occurring in predominantly female vertebrates, with endocrine disrupting and carcinogenic potential. Microbial biodegradation of estrogens is essential for their elimination from surface waters and wastewater. Aerobic bacteria employ oxygenases for the initial cleavage of the aromatic ring A. In contrast, anaerobic degradation of estrogens is initiated by methyl transfer-dependent conversion into androgens involving a putative cobalamin-dependent methyltransferase system. The methyl donor for this unprecedented reaction and its stoichiometric regeneration have remained unknown. With the biomass obtained from large-scale fermentation of an estrogen-degrading denitrifying bacterium, we identified S-adenosyl-methionine (SAM) as the methyl donor for the cobalamin-mediated methyl transfer to estrogens. To continuously supply C1 units to initiate estrogen degradation, genes for SAM regeneration from estradiol-derived catabolites are highly upregulated. Data presented here shed light into biochemical processes involved in the globally important microbial degradation of estrogens.
format	article
author	Christian Jacoby Joris Krull Jennifer Andexer Nico Jehmlich Martin von Bergen Thomas Brüls Matthias Boll
author_facet	Christian Jacoby Joris Krull Jennifer Andexer Nico Jehmlich Martin von Bergen Thomas Brüls Matthias Boll
author_sort	Christian Jacoby
title	Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria
title_short	Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria
title_full	Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria
title_fullStr	Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria
title_full_unstemmed	Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria
title_sort	channeling c1 metabolism toward <italic toggle="yes">s</italic>-adenosylmethionine-dependent conversion of estrogens to androgens in estrogen-degrading bacteria
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/010665a58f0c418c86d0559e4e0ccf02
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Channeling C1 Metabolism toward <italic toggle="yes">S</italic>-Adenosylmethionine-Dependent Conversion of Estrogens to Androgens in Estrogen-Degrading Bacteria

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