Plant N-glycan breakdown by human gut Bacteroides

Plant N-glycan breakdown by human gut Bacteroides
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人类肠道拟杆菌对植物 N-聚糖的分解

DOI:
10.1101/2022.04.07.487459
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发表时间:
2022
期刊:
--
影响因子:
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通讯作者:
Crouch L
Crouch L
中科院分区:
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作者:
Crouch L

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人类结肠微生物群可获得的主要营养素是来自饮食的复合聚糖。为了降解这种高度可变的糖结构混合物,肠道微生物已经获得了大量不同的碳水化合物活性酶(CAZymes),主要是糖苷水解酶,其中许多具有可用于一系列不同应用的特异性。植物N-聚糖普遍存在于植物产生的蛋白质中,因此也是饮食的组成部分,但肠道微生物群对这些复杂分子的分解还没有研究。植物N-聚糖也是花粉和一些植物性食品中的过敏原,当植物用于医疗应用的异源蛋白质生产时,存在的N-聚糖可能对治疗功能和稳定性构成风险。在这里,我们使用一种新的基因组关联的方法来发现酶,以确定一个gutBacteroidesspecies编码的植物复合N-聚糖的分解途径,并生化表征涉及的五种CA酶,包括PNGase和GH 92 α-甘露糖苷酶的结构。这些酶为植物N-聚糖的修饰提供了一个工具箱,用于一系列潜在的应用。此外,关键的PNGase还具有针对昆虫型N-聚糖的活性,我们从昆虫作为营养源的角度进行了讨论。
The major nutrients available to the human colonic microbiota are complex glycans derived from the diet. To degrade this highly variable mix of sugar structures, gut microbes have acquired a huge array of different carbohydrate-active enzymes (CAZymes), predominantly glycoside hydrolases, many of which have specificities that can be exploited for a range of different applications. PlantN-glycans are prevalent on proteins produced by plants and thus components of the diet, but the breakdown of these complex molecules by the gut microbiota has not been explored. PlantN-glycans are also well characterized allergens in pollen and some plant-based foods, and when plants are used in heterologous protein production for medical applications, theN-glycans present can pose a risk to therapeutic function and stability. Here we use a novel genome association approach for enzyme discovery to identify a breakdown pathway for plant complexN-glycans encoded by a gutBacteroidesspecies and biochemically characterize five CAZymes involved, including structures of the PNGase and GH92 α-mannosidase. These enzymes provide a toolbox for the modification of plantN-glycans for a range of potential applications. Furthermore, the keystone PNGase also has activity against insect-typeN-glycans, which we discuss from the perspective of insects as a nutrient source.
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