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Biological rational for the mannosidase super family in Bacteroides thetaiotaomicron (Bt alpha mannosidase)
Start date: 01 Jan 2008, End date: 31 Dec 2010 PROJECT  FINISHED 

The human intestine is colonized by over 10 trillions symbiotic bacteria which play a critical role in human health such as preventing inflammation and cancer. These microorganisms hydrolyse complex carbohydrates polymers from our diet that are not degraded by “our” own enzymes and thus, in addition to preventing cancer and inflammation, increase the nutrients available to the human host. Indeed, recent studies have shown that the composition of the microorganisms in the large intestines influences fat deposition in the mammalian host demonstrating how these bacteria can alter metabolism in their host. The symbiotic bacterium Bacteroides thetaiotaomiron is the most abundant microoganism in the large intestine. B. thetaiotaomicron, colonises the gut by accessing both human and dietary complex carbohydrates. It synthesises over 200 glycoside hydrolases which is greater than any other bacterium studied to date indicating that the microorganism exploits complex carbohydrates as an important nutrient source. Intriguingly there has been a significant expansion in glycoside hydrolase families in which the enzymes attack polymers containing the sugar mannose which is present in complex carbohydrates display on the surface of human cells. These carbohydrate structures contain three mannose molecules and are elongated with different combination of other sugars making these complex molecules highly variable. B. thetaiotaomicron produces 23 enzymes in the glycoside hydrolase family GH92 which attacks glycosidic bonds that are linked to mannose sugars and thus they are likely to target the carbohydrates on the surface of human cells. The biological rationale for such a large number of GH92 enzymes may reflect diversity of sugars attached to mannose in human complex carbohydrates. The central objective of this project is to dissect the specificity and the mechanism of carbohydrate recognition of representatives of GH92 B. thetaiotaomicron enzymes.
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