The primary focus of this research proposal will be the identification, discovery, and elucidation of novel biochemical pathways for the metabolism of complex carbohydrates in the human gut microbiome. Currently, more than one thousand different bacterial species have been identified in the human intestinal tract and the total number of genes contained within these bacteria exceeds the number of human genes by more than two orders of magnitude. Moreover, it has been demonstrated that the composition of the human gut microbiome and the associated metabolic diversity contained within these bacteria contribute significantly to the maintenance of human health and physiology. Unfortunately, a significant fraction of the enzymes and corresponding metabolic pathways contained within the bacteria found in the human gut have an uncertain, unknown, or incorrect functional annotation. This uncertainty suggests that a substantial fraction of the metabolic potential contained within the human gut microbiome remains to be properly characterized. Our proposed experimental approach for the discovery and elucidation of novel metabolic pathways for the metabolism of complex carbohydrates will involve the concerted and synergistic utilization of bioinformatics, computational biology, three-dimensional protein structure determination, metabolomics and physical screening of focused compound libraries. The determination of the substrate and reaction diversity contained within the newly discovered enzyme-catalyzed reactions will provide unique insights into the molecular mechanisms for the evolution and development of novel enzymatic activities and will provide potential targets for therapeutic intervention.

Public Health Relevance

The primary focus for the research described in this proposal will be the identification, discovery, and elucidation of novel biochemical pathways for the metabolism of complex carbohydrates in the human gut microbiome. The determination of the substrate and reaction diversity contained within these newly discovered metabolic pathways will provide unique insights into the molecular mechanisms for the evolution and development of novel enzymatic activities and will provide potential targets for direct therapeutic intervention and significant improvements in human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM122825-03
Application #
9822978
Study Section
Macromolecular Structure and Function A Study Section (MSFA)
Program Officer
Fabian, Miles
Project Start
2017-12-15
Project End
2021-11-30
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
020271826
City
College Station
State
TX
Country
United States
Zip Code
77845