Characterization of an Alternative Starch Utilization System from the Human Gut Bacterium Bacteroides thetaiotaomicron and its Implications in Human Nutrition

Abstract

Bacteroides thetaiotaomicron is a dominant member of the human gut microbiota and has been shown to play an important role in the physiological state of the human body with influences on nutrition, pathology and immunological development. This bacterium has been recorded to have an extensive array of genes involved in the acquisition and utilization of dietary and human mucosal glycans. The ability to utilization such dietary carbohydrates were first recognized with the Starch Utilization System (Sus) and demonstrated an important metabolic cascade that allows B.thetaiotaomicron to thrive in the gut. The objective of our study is to investigate an additional starch system in B.thetaiotaomicron and critically analyze its contribution to starch utilization in the human colon. This system is predicted to function similarly to Sus with outer membrane binding of starch glycans by a SusD‐homolog, transportation of glycans into the bacterial cell by a SusC‐homolog, periplasmic hydrolysis by a GH31 and GH97 glycoside hydrolases and gene up‐regulation by a Two‐Component System regulator. Using biochemical techniques, our research has demonstrated for the first time that a SusD homolog has the ability to hydrolyze starch glycans outside the cell and assist in the utilization of starch as an energy source. Furthermore, through biochemical and structural studies, we are able to show maltooligosaccharide hydrolysis from a GH31 enzyme, complemented with a GH 97 enzyme, revealing dual alpha‐glucosidic activity in the periplasm. These mechanisms demonstrate a divergence of starch utilization and further provide supporting evidence of the evolutionary advantage this bacterium has in the human colon.