# The Discovery of Novel Metabolic Pathways for the Biosynthesis and Degradation of Complex Carbohydrates within the Human Gut Microbiome

> **NIH NIH R35** · TEXAS A&M UNIVERSITY · 2021 · $346,488

## Abstract

The primary focus of this research proposal is the discovery and elucidation of novel
biochemical pathways for the biosynthesis and metabolism of complex and simple
carbohydrates in the human gut microbiome. The total number of genes contained within the
distinct bacterial species that inhabit the human gut exceeds the number of human genes by
more than two orders of magnitude. The metabolic diversity within these bacteria contributes
significantly to the maintenance of human health and physiology. Unfortunately, a significant
fraction of the enzymes and metabolic pathways contained within the bacterial species localized
in the human gut have an uncertain, unknown, or incorrect functional annotation. This
uncertainty demonstrates that a substantial fraction of the metabolic potential found within the
human gut microbiome remains to be properly characterized. The experimental approach for
the discovery and elucidation of novel biochemical pathways for the metabolism of complex
carbohydrates will employ the concerted and synergistic utilization of computational biology,
bioinformatics, three-dimensional protein structure determination, metabolomics, and physical
screening of focused compound libraries. This investigation will further be directed towards a
complete understanding of the assembly and biosynthesis of the diverse capsular
polysaccharides in the human pathogen Campylobacter jejuni, the leading cause of human
gastroenteritis world-wide. The capsular polysaccharides are important for the invasion and
colonization of the host organism and the monosaccharides that comprise the CPS in various
strains of C. jejuni are unusual and complex. This endeavor will focus on the elucidation of the
molecular pathways for the biosynthesis of the unusual array of monosaccharide building blocks
and the associated molecular logic for the directed assembly of unique polysaccharide sequences
by a series of sugar transferase enzymes. The determination of the substrate and reaction
diversity contained within these 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.

## Key facts

- **NIH application ID:** 10084621
- **Project number:** 1R35GM139428-01
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Frank M. Raushel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,488
- **Award type:** 1
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084621

## Citation

> US National Institutes of Health, RePORTER application 10084621, The Discovery of Novel Metabolic Pathways for the Biosynthesis and Degradation of Complex Carbohydrates within the Human Gut Microbiome (1R35GM139428-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10084621. Licensed CC0.

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