An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions

Po Hsiang Wang, Zong-Huei Li, Wael Ismail, Ching Yen Tsai, Ching Wen Lin, Yu Wen Tsai, Yin Ru Chiang

研究成果: 雜誌貢獻文章

16 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號e66675
期刊PLoS One
8
發行號6
DOIs
出版狀態已發佈 - 六月 24 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Wang, P. H., Li, Z-H., Ismail, W., Tsai, C. Y., Lin, C. W., Tsai, Y. W., & Chiang, Y. R. (2013). An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions. PLoS One, 8(6), [e66675]. https://doi.org/10.1371/journal.pone.0066675