Novel Biochemical Pathways for the Metabolism of Carbohydrates in the Human gut Micriobiome
Grant
Overview
Affiliation
Other
View All
Overview
abstract
The primary focus of this research proposal will be the identification, discovery, andelucidation of novel biochemical pathways for the metabolism of complex carbohydrates in the humangut microbiome. Currently, more than one thousand different bacterial species have been identified inthe human intestinal tract and the total number of genes contained within these bacteria exceeds thenumber of human genes by more than two orders of magnitude. Moreover, it has been demonstratedthat the composition of the human gut microbiome and the associated metabolic diversity containedwithin these bacteria contribute significantly to the maintenance of human health and physiology.Unfortunately, a significant fraction of the enzymes and corresponding metabolic pathways containedwithin the bacteria found in the human gut have an uncertain, unknown, or incorrect functionalannotation. This uncertainty suggests that a substantial fraction of the metabolic potential containedwithin the human gut microbiome remains to be properly characterized. Our proposed experimentalapproach for the discovery and elucidation of novel metabolic pathways for the metabolism ofcomplex carbohydrates will involve the concerted and synergistic utilization of bioinformatics,computational biology, three-dimensional protein structure determination, metabolomics andphysical screening of focused compound libraries. The determination of the substrate and reactiondiversity contained within the newly discovered enzyme-catalyzed reactions will provide uniqueinsights into the molecular mechanisms for the evolution and development of novel enzymaticactivities and will provide potential targets for therapeutic intervention.
