# Salvage of the sulfur and carbon byproducts of S-adenosylmethionine metabolism in pathogenic bacteria

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $390,000

## Abstract

Project Summary
Biologically available sulfur is essential for the synthesis of methionine (Met) and its derivative, S-adenosyl-L-
methionine (SAM). SAM is used for diverse metabolic purposes, serving primarily as a methyl donor for DNA
and protein methylation, as a 5’-deoxyadenosyl radical donor for radical-SAM reactions, as an aminopropyl donor
for polyamine synthesis and volved in the synthesis of acyl-homoserine lactone quorum sensing molecules in
bacteria. As a consequence of this metabolism, a dead-end, sulfur-containing byproduct, 5’-methylthioadenosine
(MTA) is formed. MTA is a product inhibitor of polyamine synthesis and MTA accumulation is thought to be toxic.
Since the assimilation of inorganic sulfur is energetically costly and many organisms encounter sulfur-poor
environments, maintaining or salvaging appropriate cellular organic sulfur pools is critical. Moreover, disruption
or reduced functioning of methionine salvage pathways (MSPs) has many health-related consequences
including influences on cancer cell growth and liver cirrhosis; intermediates of the pathway have also been shown
to influence apoptopic processes, while analogs of these intermediates are promising therapeutic agents. Newly
discovered MTA pathways from our laboratory, the DHAP-ethylene and methanethiol shunts, were recently
described, the genes of which appear to be widespread and selectively found among several pathogenic species.
Nonpathogenic species from these genera do not contain these genes. Thus, the hypothesis is that the shunt
genes/enzymes hold some special significance to metabolism of these pathogenic species. Moreover, the same
novel genes and enzymes were recently found to participate in radical SAM reactions to generate and metabolize
5’-deoxyadenosine (5dAdo), a structurally similar byproduct to MTA, which could potentially be recycled for
carbon salvage. The long-term goal will thus be to determine the role and physiological significance of the
DHAP/MTA/5dAdo pathways for sulfur and carbon salvage, and the potential of these pathways to influence the
successful metabolism of extraintestinal pathogenic Escherichia coli (ExPEC), including uropathogenic (UPEC)
strains which contain these genes on a specific pathogenesis island. A specific aim (Aim 1) will be to determine
the precise role of these genes and encoded enzymes and resolve further metabolic steps in sulfur/carbon
salvage via whole cell feeding experiments using radio-labeled (14C) and 13C MTA and 5dAdo metabolites in wild
type and mutant strains. These in vivo studies will be supplemented by in vitro analyses with specific enzymes.
The second aim (Aim 2) will involve resolving how these genes are genetically regulated, an important facet of
sulfur/carbon salvage in these organisms. Resolution of the specific aims of this project have considerable health
relevance as ExPEC/UPEC strains cause major health problems and infect millions of people. It is conceivable
that the identification and r...

## Key facts

- **NIH application ID:** 10399586
- **Project number:** 5R01AI154456-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Justin Andrew North
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2020-05-13 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399586

## Citation

> US National Institutes of Health, RePORTER application 10399586, Salvage of the sulfur and carbon byproducts of S-adenosylmethionine metabolism in pathogenic bacteria (5R01AI154456-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399586. Licensed CC0.

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