التفاصيل البيبلوغرافية
| العنوان: |
Substrate Inhibition of 5β-Δ4-3-Ketosteroid Dehydrogenase in Sphingobium sp. Strain Chol11 Acts as Circuit Breaker During Growth With Toxic Bile Salts |
| المؤلفون: |
Franziska M. Feller, Gina Marke, Steffen L. Drees, Lars Wöhlbrand, Ralf Rabus, Bodo Philipp |
| المصدر: |
Frontiers in Microbiology, Vol 12 (2021) |
| بيانات النشر: |
Frontiers Media S.A., 2021. |
| سنة النشر: |
2021 |
| المجموعة: |
LCC:Microbiology |
| مصطلحات موضوعية: |
bacterial metabolism, bile acid, biodegradation, dehydrogenase, flavoprotein, steroid, Microbiology, QR1-502 |
| الوصف: |
In contrast to many steroid hormones and cholesterol, mammalian bile salts are 5β-steroids, which leads to a bent structure of the steroid core. Bile salts are surface-active steroids excreted into the environment in large amounts, where they are subject to bacterial degradation. Bacterial steroid degradation is initiated by the oxidation of the A-ring leading to canonical Δ4-3-keto steroids with a double bond in the A-ring. For 5β-bile salts, this Δ4-double bond is introduced into 3-keto-bile salts by a 5β-Δ4-ketosteroid dehydrogenase (5β-Δ4-KSTD). With the Nov2c019 protein from bile-salt degrading Sphingobium sp. strain Chol11, a novel 5β-Δ4-KSTD for bile-salt degradation belonging to the Old Yellow Enzyme family was identified and named 5β-Δ4-KSTD1. By heterologous production in Escherichia coli, 5β-Δ4-KSTD function could be shown for 5β-Δ4-KSTD1 as well as the homolog CasH from bile-salt degrading Rhodococcus jostii RHA1. The deletion mutant of 5β-Δ4-kstd1 had a prolonged lag-phase with cholate as sole carbon source and, in accordance with the function of 5β-Δ4-KSTD1, showed delayed 3-ketocholate transformation. Purified 5β-Δ4-KSTD1 was specific for 5β-steroids in contrast to 5α-steroids and converted steroids with a variety of hydroxy groups regardless of the presence of a side chain. 5β-Δ4-KSTD1 showed a relatively low Km for 3-ketocholate, a very high specific activity and pronounced substrate inhibition. With respect to the toxicity of bile salts, these kinetic properties indicate that 5β-Δ4-KSTD1 can achieve fast detoxification of the detergent character as well as prevention of an overflow of the catabolic pathway in presence of increased bile-salt concentrations. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1664-302X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fmicb.2021.655312/full; https://doaj.org/toc/1664-302X |
| DOI: |
10.3389/fmicb.2021.655312 |
| URL الوصول: |
https://doaj.org/article/7abfcc29b82448a5b54165455b229d40 |
| رقم الانضمام: |
edsdoj.7abfcc29b82448a5b54165455b229d40 |
| قاعدة البيانات: |
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