Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Nat Chem Biol. 2023 Jun;19(6):778-789. doi: 10.1038/s41589-023-01272-y. Epub 2023 Mar 2.
Mucinolytic bacteria modulate host-microbiota symbiosis and dysbiosis through their ability to degrade mucin O-glycans. However, how and to what extent bacterial enzymes are involved in the breakdown process remains poorly understood. Here we focus on a glycoside hydrolase family 20 sulfoglycosidase (BbhII) from Bifidobacterium bifidum, which releases N-acetylglucosamine-6-sulfate from sulfated mucins. Glycomic analysis showed that, in addition to sulfatases, sulfoglycosidases are involved in mucin O-glycan breakdown in vivo and that the released N-acetylglucosamine-6-sulfate potentially affects gut microbial metabolism, both of which were also supported by a metagenomic data mining analysis. Enzymatic and structural analysis of BbhII reveals the architecture underlying its specificity and the presence of a GlcNAc-6S-specific carbohydrate-binding module (CBM) 32 with a distinct sugar recognition mode that B. bifidum takes advantage of to degrade mucin O-glycans. Comparative analysis of the genomes of prominent mucinolytic bacteria also highlights a CBM-dependent O-glycan breakdown strategy used by B. bifidum.
粘蛋白裂解细菌通过降解粘蛋白 O-聚糖的能力来调节宿主-微生物共生体和失调。然而，细菌酶在这个分解过程中是如何以及在何种程度上参与的，仍知之甚少。在这里，我们关注双歧双歧杆菌中的糖苷水解酶家族 20 硫酸酯酶（BbhII），它从硫酸粘蛋白中释放 N-乙酰氨基葡萄糖-6-硫酸盐。糖组学分析表明，除了硫酸酯酶外，硫酸糖苷酶也参与体内粘蛋白 O-聚糖的分解，释放的 N-乙酰氨基葡萄糖-6-硫酸盐可能影响肠道微生物代谢，这两者都得到了宏基因组数据挖掘分析的支持。BbhII 的酶学和结构分析揭示了其特异性的结构基础，以及存在一个具有独特糖识别模式的 GlcNAc-6S 特异性碳水化合物结合模块（CBM）32，双歧双歧杆菌利用它来降解粘蛋白 O-聚糖。对有代表性的粘蛋白裂解细菌基因组的比较分析也突出了双歧双歧杆菌所利用的依赖 CBM 的 O-聚糖分解策略。
