# Studies of metal-containing and metal-less EutT adenosyltransferases

> **NIH NIH F31** · UNIVERSITY OF GEORGIA · 2020 · $42,355

## Abstract

Project Summary/Abstract
Understanding the physiological context of the metabolic needs of a pathogen provides a framework for
targeted development of antimicrobials. In the case of Salmonella enterica, respiration of ethanolamine in the
intestinal environment provides a fitness advantage over commensal microorganisms. Ethanolamine
catabolism is a coenzyme B12-dependent pathway that occurs inside a proteinaceous compartment called the
ethanolamine (Eut) metabolosome. Ethanolamine is deaminated by ethanolamine ammonia lyase (EAL) to
form acetaldehyde, which eventually enters central metabolism as acetyl-CoA. EutA reactivates inactive EAL
by removing dysfunctional coenzyme B12 at the expense of ATP. These reactions are needed to trigger the
initial step of ethanolamine catabolism hence understanding the interactions required for these processes in
the context of the Eut metabolosome would provide opportunities for targeted disruption of the metabolic
pathway. There are several gaps of knowledge that need to be filled in so we can improve our understanding f
ethanolamine catabolism in this human pathogen. First, the mechanism of catalysis of the adenosyltransferase
EutT enzyme that converts vitamin B12 to coenzyme B12 is unknown, thus will be investigated. While the S.
enterica EutT is a metalloprotein, EutT homologues in some other pathogens (e.g., Listeria monocytogenes,
Clostridum tetani) function without a metal. Metal containing and metal-less Eut enzyme will be studied, and
their mechanisms of catalysis compared to elucidate the role of the metal center. Second, it is not understood
how coenzyme B12 is delivered to EAL from EutT. Preliminary evidence strongly suggests that EutA mediates
the delivery, and that EutT, EutA and EAL may form a complex. A multidisciplinary approach (crystallography,
spectroscopy, molecular biology, biochemistry, in vivo genetics, and physiology) will be used to address this
complex problem. Collectively, this work will advance our understanding of how cells synthesize and deliver
essential coenzymes to the enzymes that use them, in this case inside a cellular compartment.

## Key facts

- **NIH application ID:** 10058537
- **Project number:** 3F31GM122394-03S1
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Flavia Gisela Costa
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $42,355
- **Award type:** 3
- **Project period:** 2017-02-01 → 2020-12-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058537

## Citation

> US National Institutes of Health, RePORTER application 10058537, Studies of metal-containing and metal-less EutT adenosyltransferases (3F31GM122394-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10058537. Licensed CC0.

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