Complex pectin metabolism by gut bacteria reveals novel catalytic functions

The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet. The hierarchical deconstruction of the complex pectic glycan rhamnogalacturonan-II by the human gut bacterium Bacteroides thetaiotaomicron reveals seven new families of glycoside hydrolases and three catalytic functions not previously observed. Pectin breakdown in the gut Rhamnogalacturonan-II (RG-II) is the most complex glycan known. It has been a feature of the human diet since the time of the Neanderthals, but the mechanism by which this polysaccharide is broken down is unknown. In this work, the authors dissect the key processes and enzyme families in the gut that are involved in RG-II deconstruction. A single gut bacteria from the Bacteroides phylum metabolizes this complex substrate by cleaving all but one of the 21 glycosidic linkages. This degradation process involves seven newly discovered families of glycoside hydrolases, as well as novel catalytic functions of several known enzymes. This work delves deep into the mechanisms of glycan degradation by bacteria in the human gut microbiota and how they have evolved with this degradation to utilize rare sugars.