Initial steps in anoxic testosterone degradation by Steroidobacter denitrificans

Chiang, Yin-Ru; Fang, Jia You; Ismail, Wael; Wang, Po Hsiang

doi:10.1099/mic.0.037788-0

Cited by 34 publications

(20 citation statements)

References 26 publications

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“…The S. denitrifi cans was grown with 4 mM of unlabeled testosterone at 28°C in anoxic fed-batch cultures (2 l) according to published procedures ( 20 ). The amounts of residual testosterone in the anoxic culture were monitored using HPLC.…”

Section: Anaerobic Growth Of S Denitrifi Cans With Unlabeled Testostmentioning

confidence: 99%

“…Recently, the initial reactions involved in the anaerobic metabolism of cholesterol and testosterone were reported (19)(20)(21), albeit the ring cleavage details of the anaerobic pathways are yet to be unraveled. In this study, we adopted a 13 C metabolomic approach to investigate the anaerobic degradation of testosterone using S. denitrifi cans as a model organism.…”

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confidence: 99%

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Anaerobic and aerobic cleavage of the steroid core ring structure by Steroidobacter denitrificans

Wang

Leu

Ismail

et al. 2013

Journal of Lipid Research

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Section: Anaerobic Growth Of S Denitrifi Cans With Unlabeled Testostmentioning

confidence: 99%

mentioning

confidence: 99%

Anaerobic and aerobic cleavage of the steroid core ring structure by Steroidobacter denitrificans

Wang

Leu

Ismail

et al. 2013

Journal of Lipid Research

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“…In our previous study, we showed that S. denitrificans should be able to anaerobically degrade testosterone using a stoichiometric method. However, the possibility of partial oxidation of testosterone by our model organism could not be excluded (5). We presented here clear and direct evidence to show that testosterone was mineralized to CO 2 during the denitrifying growth of S. denitrificans (Fig.…”

Section: Resultsmentioning

confidence: 53%

“…One of them, Steroidobacter denitrificans DSMZ18526, can anaerobically utilize certain C 18 estrogen or C 19 androgen steroids as the sole carbon and energy source via an unknown catabolic pathway (10). Recently, we reported on the initial steps in the anoxic catabolism of testosterone by this denitrifying bacterium (5). We demonstrated that under anoxic conditions, S. denitrificans initially oxidizes testosterone to 1-dehydrotestosterone, which is then transformed to androsta-1,4-diene-3,17-dione.…”

mentioning

confidence: 99%

“…Large-scale fed-batch cultures were carried out in 5-liter glass bottles sealed with rubber stoppers. The medium and method used for the cultivation of S. denitrificans under denitrifying conditions are described elsewhere (5). Cells were harvested by centrifugation in the exponential growth phase at an optical density at 600 nm (OD 600 ) of 0.8 to 1.0 (optical path, 1 cm), and the cell pellet was then stored at Ϫ80°C.…”

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confidence: 99%

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A Novel Testosterone Catabolic Pathway in Bacteria

et al. 2011

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Forty years ago, Coulter and Talalay (A. W. Coulter and P. Talalay, J. Biol. Chem. 243:3238-3247, 1968) established the oxygenase-dependent pathway for the degradation of testosterone by aerobes. The oxic testosterone catabolic pathway involves several oxygen-dependent reactions and is not available for anaerobes. Since then, a variety of anaerobic bacteria have been described for the ability to degrade testosterone in the absence of oxygen. Here, a novel, oxygenase-independent testosterone catabolic pathway in such organisms is described. Steroidobacter denitrificans DSMZ18526 was shown to be capable of degrading testosterone in the absence of oxygen and was selected as the model organism in this study. In a previous investigation, we identified the initial intermediates involved in an anoxic testosterone catabolic pathway, most of which are identical to those of the oxic pathway demonstrated in Comamonas testosteroni. In this study, five additional intermediates of the anoxic pathway were identified. We demonstrated that subsequent steps of the anoxic pathway greatly differ from those of the established oxic pathway, which suggests that a novel pathway for testosterone catabolism is present. In the proposed anoxic pathway, a reduction reaction occurs at C-4 and C-5 of androsta-1,4-diene-3,17-dione, the last common intermediate of both the oxic and anoxic pathways. After that, a novel hydration reaction occurs and a hydroxyl group is thus introduced to the C-1␣ position of C 19 steroid substrates. To our knowledge, an enzymatic hydration reaction occurring at the A ring of steroid compounds has not been reported before.

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Gut microbial 3α‐hydroxysteroid dehydrogenase promotes depression in males via degrading testosterone

Li,

Cheng,

Zhang

et al. 2024

Interdisciplinary Medicine

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Abnormal gut microbiota is associated with the occurrence of depression, but the specific pathophysiological role of gut microbiota in the pathogenesis of depression is still unknown. We found that the levels of serum steroid hormone testosterone in male patients with depression were lower than in healthy controls. Using testosterone as the only carbon source, the testosterone‐degrading bacteria Arthrobacter koreensis was isolated from fecal of low testosterone male patients with depression. We found that A. koreensis administration in mice led to reduced serum testosterone levels and depression‐like behaviors, which were improved by antibiotic treatment. Using whole genome sequencing, the gene mediating testosterone degradation in A. koreensis was identified and annotated as 3α‐hydroxysteroid dehydrogenase (3α‐HSD). Escherichia coli heterologously expressing 3α‐HSD obtained the capacity to degrade testosterone, causing depression‐like behaviors after gavage to mice. Testosterone supplementation improves depression‐like behavior in mice induced by gavage of Escherichia coli heterologously expressing 3α‐HSD. Finally, the universality of 3α‐HSD in gut of male patients with depression was higher than that of healthy controls. Overall, our results revealed a new pathway that potentially links testosterone degradation by gut microbes harboring 3α‐HSD enzymes to the pathogenesis of depression. Gut microbial 3α‐HSD can induce depression in mice via testosterone degradation. This means that 3α‐HSD expressed by gut bacteria may be a potential target for depression in men.

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Initial steps in anoxic testosterone degradation by Steroidobacter denitrificans

Cited by 34 publications

References 26 publications

Anaerobic and aerobic cleavage of the steroid core ring structure by Steroidobacter denitrificans

Anaerobic and aerobic cleavage of the steroid core ring structure by Steroidobacter denitrificans

A Novel Testosterone Catabolic Pathway in Bacteria

Gut microbial 3α‐hydroxysteroid dehydrogenase promotes depression in males via degrading testosterone

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