# Project 1 - Exploiting Metabolic  Vulnerabilities

> **NIH NIH P01** · TEXAS A&M AGRILIFE RESEARCH · 2021 · $647,642

## Abstract

Project Summary – Project 1 - Exploiting metabolic vulnerabilities
Central metabolic pathways are critical for bacterial viability and represent a rich source of potential drug
targets. However, these enzymes have been under-exploited by anti-bacterial drug development
programs for two basic reasons. Firstly, these complex pathways perform diverse roles under different
growth states, leaving their importance during infection unclear. In addition, homologous mammalian
enzymes often exist, necessitating the design of specific inhibitors. To overcome these complications
and exploit this rich source of potential drug targets, we use a combination of genetics and chemical
biology to identify druggable metabolic enzymes that are essential in relevant host microenvironments,
and employ structural biology to aid in the development of specific inhibitors. These studies have defined
target-inhibitor pairs in a broad range of metabolic pathways and regulators. For example, central carbon
metabolic enzymes critical for bacterial survival in animal models, such as phophoenolpyruvate
carboxykinase (PEPCK), pyruvate kinase (PK), and malate dehydrogenase, have been subjected to
structure-guided inhibitor design. Similar approaches have been applied to critical components of lipid
anabolic pathways, such as PKS13 and components of acyl-CoA carboxylase complexes, enzymes
critical for amino acid and cofactor synthesis, and heme metabolism. These studies have identified potent
and specific small molecule inhibitors, revealed novel protein complexes and elucidated the physiological
functions of these enzymes in the bacterium.

## Key facts

- **NIH application ID:** 10242862
- **Project number:** 5P01AI095208-08
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** CHRISTOPHER M SASSETTI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $647,642
- **Award type:** 5
- **Project period:** 2012-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242862

## Citation

> US National Institutes of Health, RePORTER application 10242862, Project 1 - Exploiting Metabolic  Vulnerabilities (5P01AI095208-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242862. Licensed CC0.

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