An oxygenase-independent cholesterol catabolic pathway operates under oxic conditions.
An oxygenase-independent cholesterol catabolic pathway operates under oxic conditions.
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DOI：
10.1371/journal.pone.0066675
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chiang YR
中科院分区：
文献类型：
--
作者：
Wang PH;Lee TH;Ismail W;Tsai CY;Lin CW;Tsai YW;Chiang YR
胆固醇是自然界中最普遍存在的化合物之一。胆固醇有氧降解的9，10-seco途径是在30年前建立的。该途径的特征在于广泛使用氧和加氧酶进行底物活化和环分裂。经典途径是所有胆固醇降解菌研究中唯一采用的分解代谢途径。无论是否存在氧气，Sterolibacterium cafficans都可以降解胆固醇。在这里，我们用13 C标记的胆固醇有氧培养模型生物，并随时间监测底物消耗和中间产物的产生。基于检测到的13 C标记的中间体，本研究提出了一种替代的胆固醇分解代谢途径。这种替代途径在许多重要方面不同于经典的9，10-seco-途径。首先，底物活化通过厌氧C-25羟基化和随后的异构化进行以形成26-羟基胆甾-4-烯-3-酮。第二，在侧链降解后，通过向C-1/C-2双键添加水来活化所得雄激素中间体。第三，核心环结构的裂解通过水解机制在A环开始。18 O掺入实验证实，水是唯一的氧供体在这一分解代谢途径。
Cholesterol is one of the most ubiquitous compounds in nature. The 9,10-seco-pathway for the aerobic degradation of cholesterol was established thirty years ago. This pathway is characterized by the extensive use of oxygen and oxygenases for substrate activation and ring fission. The classical pathway was the only catabolic pathway adopted by all studies on cholesterol-degrading bacteria. Sterolibacterium denitrificans can degrade cholesterol regardless of the presence of oxygen. Here, we aerobically grew the model organism with 13C-labeled cholesterol, and substrate consumption and intermediate production were monitored over time. Based on the detected 13C-labeled intermediates, this study proposes an alternative cholesterol catabolic pathway. This alternative pathway differs from the classical 9,10-seco-pathway in numerous important aspects. First, substrate activation proceeds through anaerobic C-25 hydroxylation and subsequent isomerization to form 26-hydroxycholest-4-en-3-one. Second, after the side chain degradation, the resulting androgen intermediate is activated by adding water to the C-1/C-2 double bond. Third, the cleavage of the core ring structure starts at the A-ring via a hydrolytic mechanism. The 18O-incorporation experiments confirmed that water is the sole oxygen donor in this catabolic pathway.
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影响因子：
56.9
作者：
JOHNSON, DF;BENNETT, RD;HEFTMANN, E
通讯作者：
HEFTMANN, E
影响因子：
3.2
作者：
Leu, Yann-Lii;Wang, Po-Hsiang;Chiang, Yin-Ru
通讯作者：
Chiang, Yin-Ru
影响因子：
2.8
作者：
RABUS, R;WIDDEL, F
通讯作者：
WIDDEL, F
DOI：
10.1080/00021369.1969.10859516
发表时间：
1969-01-01
期刊：
AGRICULTURAL AND BIOLOGICAL CHEMISTRY
影响因子：
--
作者：
ARIMA, K;NAGASAWA, M;TAMURA, G
通讯作者：
TAMURA, G
影响因子：
4.8
作者：
Capyk, Jenna K.;D'Angelo, Igor;Eltis, Lindsay D.
通讯作者：
Eltis, Lindsay D.