A Novel Testosterone Catabolic Pathway in Bacteria
A Novel Testosterone Catabolic Pathway in Bacteria
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DOI：
10.1128/jb.00331-11
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发表时间：
2011-09-01
影响因子：
3.2
通讯作者：
Chiang, Yin-Ru
中科院分区：
文献类型：
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作者：
Leu, Yann-Lii;Wang, Po-Hsiang;Chiang, Yin-Ru
40年前，Coulter和Talalay(A.W.Coulter和P.Talalay，J.Biol.化学。243：3238-3247,1968)为需氧菌降解睾酮建立了依赖氧合酶的途径。氧化的睾酮分解代谢途径涉及几个氧依赖反应，对厌氧菌是不可用的。从那时起，各种厌氧细菌被描述为在缺乏氧气的情况下降解睾丸素的能力。在这里，描述了一种新的，不依赖于加氧酶的睾酮分解代谢途径。脱氮类杆菌DSMZ18526具有在缺氧条件下降解睾酮的能力，并被选为本研究的模式生物。在之前的研究中，我们确定了参与缺氧性睾酮分解代谢途径的初始中间体，其中大部分与Comamonas testosteroni中展示的氧化途径相同。在这项研究中，还鉴定了缺氧途径的另外五个中间体。我们证明了缺氧途径的后续步骤与已建立的氧化途径的步骤有很大的不同，这表明存在一种新的睾酮分解代谢途径。在所提出的缺氧途径中，雄烯-1，4-二烯-3，17-二酮的C-4和C-5发生还原反应，这是氧化和缺氧途径的最后一个共同中间体。之后，发生了一种新的水合反应，从而在C(19)类固醇底物的C-1α位置引入了羟基。据我们所知，发生在A环的类固醇化合物的酶促水合反应以前没有报道过。
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 alpha 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.