Hydroxysteroid dehydrogenases (HSDs) in bacteria - A bioinformatic perspective
Hydroxysteroid dehydrogenases (HSDs) in bacteria - A bioinformatic perspective
复制标题
DOI：
10.1016/j.jsbmb.2011.08.002
复制
发表时间：
2012-03-01
影响因子：
4.1
通讯作者：
Maser, Edmund
中科院分区：
文献类型：
--
作者：
Kisiela, Michael;Skarka, Adam;Maser, Edmund
甾体化合物包括胆固醇、胆汁酸和类固醇激素在多种生理过程中发挥核心作用，如细胞信号传导、生长、繁殖和能量稳态。羟基类固醇脱氢酶（HSDs）属于短链脱氢/还原酶（SDR）或醛酮还原酶（AKR）超家族，是参与类固醇激素代谢的重要酶。hsd作为一种酶开关，控制受体活性类固醇进入核激素受体，从而介导类固醇反应的微调。本研究的目的是在所有完整测序的细菌基因组中鉴定分类功能hsd并对这些蛋白质进行生物信息学注释，然后进行系统发育分析。对于生物信息学注释，我们采用迭代方法构建了特定的隐马尔可夫模型，为hsd的特定催化基团提供了可靠的识别。本文对SDRs超家族中的3 α -、7 α -、12 α - hsd和另外两种功能相关酶(3-酮类固醇- δ(1)-脱氢酶、3-酮类固醇- δ （4)(5 α)-脱氢酶）进行了详细的系统发育分析。对于一些先前报道具有特定HSD活性的细菌，我们可以注释相应的HSD蛋白。经鉴定表达HSDs的主要门是放线菌门、变形菌门和厚壁菌门。此外，还发现了一些进化上更古老的微生物（如蓝藻和Euryachaeota）。大量表达hsd的细菌构成了正常的人类胃肠道菌群。另一组细菌最初是从海水、土壤、海洋和永久冻土沉积物等自然栖息地中分离出来的。这些细菌包括多环芳烃降解物种，如假单胞菌、伯克霍尔德菌和红球菌。综上所述，HSDs存在于包括细菌和古细菌在内的多种微生物中，表明类固醇代谢是一种进化保守的机制，可能具有营养供应和信号传导等不同功能。关于类固醇和微生物的特刊文章。(C) 2011 Elsevier Ltd.版权所有。
Steroidal compounds including cholesterol, bile acids and steroid hormones play a central role in various physiological processes such as cell signaling, growth, reproduction, and energy homeostasis. Hydroxysteroid dehydrogenases (HSDs), which belong to the superfamily of short-chain dehydrogenases/reductases (SDR) or aldo-keto reductases (AKR), are important enzymes involved in the steroid hormone metabolism. HSDs function as an enzymatic switch that controls the access of receptor-active steroids to nuclear hormone receptors and thereby mediate a fine-tuning of the steroid response. The aim of this study was the identification of classified functional HSDs and the bioinformatic annotation of these proteins in all complete sequenced bacterial genomes followed by a phylogenetic analysis. For the bioinformatic annotation we constructed specific hidden Markov models in an iterative approach to provide a reliable identification for the specific catalytic groups of HSDs. Here, we show a detailed phylogenetic analysis of 3 alpha-, 7 alpha-, 12 alpha-HSDs and two further functional related enzymes (3-ketosteroid-Delta(1)-dehydrogenase, 3-ketosteroid-Delta(4)(5 alpha)-dehydrogenase) from the superfamily of SDRs. For some bacteria that have been previously reported to posses a specific HSD activity, we could annotate the corresponding HSD protein. The dominating phyla that were identified to express HSDs were that of Actinobacteria, Proteobacteria, and Firmicutes. Moreover, some evolutionarily more ancient microorganisms (e.g., Cyanobacteria and Euryachaeota) were found as well. A large number of HSD-expressing bacteria constitute the normal human gastro-intestinal flora. Another group of bacteria were originally isolated from natural habitats like seawater, soil, marine and permafrost sediments. These bacteria include polycyclic aromatic hydrocarbons-degrading species such as Pseudomonas, Burkholderia and Rhodococcus. In conclusion, HSDs are found in a wide variety of microorganisms including bacteria and archaea, suggesting that steroid metabolism is an evolutionarily conserved mechanism that might serve different functions such as nutrient supply and signaling.Article from a special issue on steroids and microorganisms. (C) 2011 Elsevier Ltd. All rights reserved.