A Novel Steroid-Coenzyme A Ligase from Novosphingobium sp. Strain Chol11 Is Essential for an Alternative Degradation Pathway for Bile Salts
A Novel Steroid-Coenzyme A Ligase from Novosphingobium sp. Strain Chol11 Is Essential for an Alternative Degradation Pathway for Bile Salts
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来自 Novosphingobium sp 菌株 Chol11 的新型类固醇辅酶 A 连接酶对于胆汁盐的替代降解途径至关重要
DOI：
10.1128/aem.01492-17
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发表时间：
2017
影响因子：
4.4
通讯作者：
B. Philipp
中科院分区：
文献类型：
--
作者：
O. Yücel;J. Holert;K.C. Ludwig;S. Thierbach;B. Philipp
胆酸盐，如胆酸盐，是带有C5羧基侧链的类固醇化合物，广泛存在于脊椎动物中。胆盐一旦排泄到土壤和水中，就可以作为各种细菌的生长底物。Novphingobium sp.Chol11菌株通过3-酮-7-脱氧-Δ4，6代谢产物，通过7-α-羟基类固醇脱水酶Hsh2催化7-羟基脱水来降解7-羟基胆盐。在其他类固醇降解菌所使用的9-10-Seco降解途径中没有观察到这种反应，这表明菌株Chol11使用了另一种途径。BLASTp分析表明，在Chol11菌株的基因组中未发现来自其他胆酸降解菌(Pseudomonas stutzeri Chol1、Comamonas testosteroni CNB-2和Rhodorics jostii RHA1)的已知侧链降解基因。菌株Chol11的一个转座子突变体对胆酸引起的生长变化进行了鉴定，鉴定出一种新的类固醇-24-甲酰辅酶A连接酶，命名为SclA。未标记的sclA缺失导致胆酸盐显著降低细胞生长速度，而含C3侧链或不含C3侧链的类固醇激素对细胞生长无影响。具有7-脱氧-3-酮-Δ4，6结构的中间体，如3，12-二氧代-4，6-胆二烯酸可能是SclA的生理底物。此外，还鉴定了一种新的依赖辅酶A(CoA)的DOCDA降解代谢物，其侧链上有一个额外的双键。这些结果支持了诺氏菌属(Novphingobium sp.Chol11菌株具有另一种降解胆酸的途径，其中侧链的降解是由CoA连接酶SclA启动的，并通过与其他类固醇降解细菌不同的未知酶催化的反应步骤进行。对这些途径的了解有助于理解全球碳循环中二氧化碳释放的部分。此外，它还有助于研究药物类固醇在环境中的去向，其中一些可能会作为内分泌干扰物。
Bile salts such as cholate are steroid compounds with a C5carboxylic side chain and occur ubiquitously in vertebrates. Upon their excretion into soils and waters, bile salts can serve as growth substrates for diverse bacteria. Novosphingobium sp. strain Chol11 degrades 7-hydroxy bile salts via 3-keto-7-deoxy-Δ4,6metabolites by the dehydration of the 7-hydroxyl group catalyzed by the 7α-hydroxysteroid dehydratase Hsh2. This reaction has not been observed in the well-studied 9-10-seco degradation pathway used by other steroid-degrading bacteria indicating that strain Chol11 uses an alternative pathway. A reciprocal BLASTp analysis showed that known side chain degradation genes from other cholate-degrading bacteria (Pseudomonas stutzeri Chol1, Comamonas testosteroni CNB-2, and Rhodococcus jostii RHA1) were not found in the genome of strain Chol11. The characterization of a transposon mutant of strain Chol11 showing altered growth with cholate identified a novel steroid-24-oyl–coenzyme A ligase named SclA. The unmarked deletion ofsclAresulted in a strong growth rate decrease with cholate, while growth with steroids with C3side chains or without side chains was not affected. Intermediates with a 7-deoxy-3-keto-Δ4,6structure, such as 3,12-dioxo-4,6-choldienoic acid (DOCDA), were shown to be likely physiological substrates of SclA. Furthermore, a novel coenzyme A (CoA)-dependent DOCDA degradation metabolite with an additional double bond in the side chain was identified. These results support the hypothesis that Novosphingobium sp. strain Chol11 harbors an alternative pathway for cholate degradation, in which side chain degradation is initiated by the CoA ligase SclA and proceeds via reaction steps catalyzed by so-far-unknown enzymes different from those of other steroid-degrading bacteria.IMPORTANCEThis study provides further evidence of the diversity of metabolic pathways for the degradation of steroid compounds in environmental bacteria. The knowledge about these pathways contributes to the understanding of the CO2-releasing part of the global C cycle. Furthermore, it is useful for investigating the fate of pharmaceutical steroids in the environment, some of which may act as endocrine disruptors.
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影响因子：
5.3
作者：
Yang, Meng;Lu, Rui;Guja, Kip E.;Wipperman, Matthew F.;St Clair, Johnna R.;Bonds, Amber C.;Garcia-Diaz, Miguel;Sampson, Nicole S.
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
6.4
作者：
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通讯作者：
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