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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere66675
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 24 2013

Fingerprint

Oxygenases
oxygenases
Cholesterol
cholesterol
Oxygen
oxygen
Sterolibacterium denitrificans
Substrates
Chemical activation
Degradation
Hydroxylation
degradation
Water
isomerization
hydroxylation
Isomerization
androgens
Androgens
Bacteria
water

ASJC Scopus subject areas

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

Cite this

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

An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions. / Wang, Po Hsiang; Li, Zong-Huei; Ismail, Wael; Tsai, Ching Yen; Lin, Ching Wen; Tsai, Yu Wen; Chiang, Yin Ru.

In: PLoS One, Vol. 8, No. 6, e66675, 24.06.2013.

Research output: Contribution to journalArticle

Wang, PH, Li, Z-H, Ismail, W, Tsai, CY, Lin, CW, Tsai, YW & Chiang, YR 2013, 'An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions', PLoS One, vol. 8, no. 6, e66675. https://doi.org/10.1371/journal.pone.0066675
Wang, Po Hsiang ; Li, Zong-Huei ; Ismail, Wael ; Tsai, Ching Yen ; Lin, Ching Wen ; Tsai, Yu Wen ; Chiang, Yin Ru. / An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions. In: PLoS One. 2013 ; Vol. 8, No. 6.
@article{e1b66d32c2984b79975e05114fe9c2f0,
title = "An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions",
abstract = "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.",
author = "Wang, {Po Hsiang} and Zong-Huei Li and Wael Ismail and Tsai, {Ching Yen} and Lin, {Ching Wen} and Tsai, {Yu Wen} and Chiang, {Yin Ru}",
year = "2013",
month = "6",
day = "24",
doi = "10.1371/journal.pone.0066675",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - An Oxygenase-Independent Cholesterol Catabolic Pathway Operates under Oxic Conditions

AU - Wang, Po Hsiang

AU - Li, Zong-Huei

AU - Ismail, Wael

AU - Tsai, Ching Yen

AU - Lin, Ching Wen

AU - Tsai, Yu Wen

AU - Chiang, Yin Ru

PY - 2013/6/24

Y1 - 2013/6/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84879482851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879482851&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0066675

DO - 10.1371/journal.pone.0066675

M3 - Article

C2 - 23826110

AN - SCOPUS:84879482851

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e66675

ER -