Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK.
Cell Rep. 2017 Oct 10;21(2):417-430. doi: 10.1016/j.celrep.2017.09.049.
Microbial utilization of complex polysaccharides is a major driving force in shaping the composition of the human gut microbiota. There is a growing appreciation that finely tuned polysaccharide utilization loci enable ubiquitous gut Bacteroidetes to thrive on the plethora of complex polysaccharides that constitute "dietary fiber." Mixed-linkage β(1,3)/β(1,4)-glucans (MLGs) are a key family of plant cell wall polysaccharides with recognized health benefits but whose mechanism of utilization has remained unclear. Here, we provide molecular insight into the function of an archetypal MLG utilization locus (MLGUL) through a combination of biochemistry, enzymology, structural biology, and microbiology. Comparative genomics coupled with growth studies demonstrated further that syntenic MLGULs serve as genetic markers for MLG catabolism across commensal gut bacteria. In turn, we surveyed human gut metagenomes to reveal that MLGULs are ubiquitous in human populations globally, which underscores the importance of gut microbial metabolism of MLG as a common cereal polysaccharide.
微生物对复杂多糖的利用是塑造人类肠道微生物组组成的主要驱动力。人们越来越认识到,精细调节的多糖利用基因座使普遍存在的肠道拟杆菌能够在构成“膳食纤维”的大量复杂多糖上茁壮成长。混合链接β(1,3)/β(1,4)-葡聚糖(MLG)是植物细胞壁多糖的一个主要家族,具有公认的健康益处,但它们的利用机制仍不清楚。在这里,我们通过生物化学、酶学、结构生物学和微生物学的结合,提供了对典型 MLG 利用基因座(MLGUL)功能的分子见解。比较基因组学结合生长研究进一步表明,同线性 MLGUL 作为共生肠道细菌中 MLG 分解代谢的遗传标记。反过来,我们调查了人类肠道宏基因组,揭示了 MLGUL 在全球人类群体中普遍存在,这强调了肠道微生物对 MLG 作为一种常见谷物多糖的代谢的重要性。