期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：39
DOI：10.1073/pnas.2208168119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
N-glycans are common posttranslational modifications on plant proteins, particularly secreted proteins. As plants are the major component of the human diet, and especially in high-fiber diets, plant
N-glycans are prominent in the gut. Despite their ubiquity in the gut, the degradation of plant
N-glycans by the microbiota has not been described. Here we used a functional analysis approach, coupled to detailed biochemistry and structural biology, to reveal a pathway for the degradation of plant
N-glycans encoded by the human gut microbiota. The work reveals insight into how our gut microbes use plant
N-glycans as a nutrient source and also provides tools to modify plant
N-glycans to mitigate allergic responses, either from foods or plant-expressed therapeutics.
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. Plant
N-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. Plant
N-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, the
N-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 complex
N-glycans encoded by a gut
Bacteroides species and biochemically characterize five CAZymes involved, including structures of the PNGase and GH92 α-mannosidase. These enzymes provide a toolbox for the modification of plant
N-glycans for a range of potential applications. Furthermore, the keystone PNGase also has activity against insect-type
N-glycans, which we discuss from the perspective of insects as a nutrient source.
