# Toward understanding the chemistry and biology of microbial DXP synthase

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $398,904

## Abstract

PROJECT SUMMARY
Microbial metabolic function and adaptability are important in many facets of human health and
disease. This proposal centers on studies of the microbial metabolic enzyme 1-deoxy-D-xylulose
5-phosphate synthase (DXPS). DXPS catalyzes the thiamin diphosphate (ThDP)-dependent
synthesis of the essential metabolite DXP, which is found in the gut microbiota, pathogenic
bacteria and parasites, but not in humans. Positioned at a metabolic branchpoint, DXP serves as
a precursor to indispensable isoprenoids and vitamins, thus, we postulate DXPS plays key roles
in microbiome function and microbial metabolic adaptation. Our long-term goal is to learn how
microbes use DXPS in different contexts, toward understanding its roles in the microbiome and
its potential as an antimicrobial target. Our group discovered a unique ligand-gated mechanism
used by DXPS that bestows targets for selective inhibition and may enable DXPS to sense and
respond to its environment. The goals of this proposal are to dissect how DXPS responds to
molecular cues, examine this sensing mechanism in different chemical contexts, and establish
novel inhibition strategies that target this distinctive feature of DXPS. Insights gained from this
research will direct our thinking about DXPS function, and guide development of chemical probes
needed to study DXPS roles in microbes.

## Key facts

- **NIH application ID:** 10876501
- **Project number:** 5R01GM143810-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Caren L. Freel Meyers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $398,904
- **Award type:** 5
- **Project period:** 2021-09-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876501

## Citation

> US National Institutes of Health, RePORTER application 10876501, Toward understanding the chemistry and biology of microbial DXP synthase (5R01GM143810-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876501. Licensed CC0.

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