Mining the human gut microbiome identifies mycobacterial d-arabinan degrading enzymes
Mining the human gut microbiome identifies mycobacterial d-arabinan degrading enzymes
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挖掘人类肠道微生物群识别分枝杆菌 d-阿拉伯聚糖降解酶
DOI：
10.1101/2022.07.22.500997
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Al-Jourani O
中科院分区：
文献类型：
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作者：
Al-Jourani O
细菌细胞壁的分裂和降解需要无数酶的协调作用。这尤其适用于抗酸生物的精细细胞壁，如结核分枝杆菌，它由多层细胞壁组成，含有一种称为阿拉伯半乳聚糖的不寻常聚糖。以前在任何生物体中都没有发现过能切割这种结构的d-阿拉伯聚糖核心的酶。我们已经询问了人类肠道微生物群表达的各种碳水化合物降解酶，并发现了四个能够降解阿拉伯半乳聚糖的d-阿拉伯聚糖或半乳聚糖组分的糖苷水解酶家族。使用来自肠道细菌的新型外切-d-呋喃半乳糖苷酶，我们产生了富集阿拉伯聚糖，并用它来鉴定D.一种D-阿拉伯聚糖降解剂。这使得能够发现切割D-阿拉伯聚糖的内切和外切作用酶。我们已经鉴定了DUF 2961家族的新成员（GH 172），和显示内切-d-阿拉伯呋喃酶活性的糖苷水解酶的新家族（DUF 4185）。DUF 4185酶在分枝杆菌中是保守的，并在许多微生物中发现，这表明降解分枝杆菌聚糖的能力在不同生物体的生物学中起着重要作用。所有分枝杆菌编码两种保守的内切-D-阿拉伯聚糖酶，其对含D-阿拉伯聚糖的细胞壁组分阿拉伯半乳聚糖和脂阿拉伯甘露聚糖显示不同的偏好，这表明它们对细胞壁修饰和/或降解是重要的。这些酶的发现将支持未来对分枝杆菌细胞壁结构和功能的研究。
Division and degradation of bacterial cell walls requires coordinated action of a myriad of enzymes. This particularly applies to the elaborate cell walls of acid-fast organisms such asMycobacterium tuberculosis, which consist of a multi-layered cell wall that contains an unusual glycan called arabinogalactan. Enzymes that cleave thed-arabinan core of this structure have not previously been identified in any organism. We have interrogated the diverse carbohydrate degrading enzymes expressed by the human gut microbiota and uncovered four families of glycoside hydrolases with the capability to degrade thed-arabinan ord-galactan components of arabinogalactan. Using novel exo-d-galactofuranosidases from gut bacteria we generated enrichedd-arabinan and used it to identifyD. gadeias a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan. We have identified new members of the DUF2961 family (GH172), and a novel family of glycoside hydrolases (DUF4185) that display endo-d-arabinofuranase activity. The DUF4185 enzymes are conserved in mycobacteria and found in many microbes, suggesting that the ability to degrade mycobacterial glycans plays an important role in the biology of diverse organisms. All mycobacteria encode two conserved endo-d-arabinanases that display different preferences for thed-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall.