# Enzymatic Determinants of Gut Microbial Metabolic Biotransformations

> **NIH NIH R35** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $390,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The human gut is a complex ecosystem, where trillions of microbes interact with dietary and host-derived
molecules, mediating biotransformations that significantly affect both the microbial community and their human
hosts. Central to this metabolic interplay are ene-reductases, a versatile class of oxidoreductases that facilitate
the reduction of carbon-carbon double bonds to single bonds. Stool metabolomics data implicates the existence
of numerous unidentified ene-reductases, constituting a gap in our understanding of gut microbial metabolism.
While these enzymes are pivotal in modulating metabolite bioavailability, impacting both microbial physiology
and human health, most remain unidentified. This research proposal aims to systematically characterize novel
gut microbial ene-reductases based on the hypothesis that these enzymes play a critical role in shaping the
chemical milieu of the gut. To achieve this goal, we will develop a platform that fuses microbiology, biochemistry,
and bioinformatics in a four-stage strategy to systematically identify and characterize gut microbial ene-
reductases responsible for the reduction of a target metabolite. First, we will identify microbial strains capable of
metabolite reduction. Second, we will identify candidate reductase genes through comparative genomics and
RNA-seq. Third, we will experimentally validate the candidate enzymes for their reductase activity. Fourth,
studies will be performed to understand the mechanistic basis of the novel enzymes. Through this research, we
aim to deepen our understanding of the chemical dialogues occurring between gut microbes and their host.
Specifically, the study will illuminate the roles that ene-reductases play in performing consequential
biotransformations and shaping microbiome community structure. While this proposal focuses on fundamental
characterization of key gut microbial enzymes, it lays the groundwork for translational advancement by
uncovering metabolic mechanisms that will ultimately facilitate precise, personalized microbiome modulation.

## Key facts

- **NIH application ID:** 10941362
- **Project number:** 1R35GM155208-01
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** A. Brantley Hall
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941362

## Citation

> US National Institutes of Health, RePORTER application 10941362, Enzymatic Determinants of Gut Microbial Metabolic Biotransformations (1R35GM155208-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10941362. Licensed CC0.

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