# Study of queuosine salvage and  function in eukaryotes; a forgotten micronutrient

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $382,850

## Abstract

Queuine is a largely forgotten bacterial-derived micronutrient that is obtained exclusively from
the gut; a preeminent small-molecule of the gut-brain axis. Our contention is that queuine is
important in metabolism and development—mammals are born sterile and queuine free—and
induces long-lasting effects into adulthood, particularly in the brain. At least 5 unique enzyme
activities are involved in queuine utilisation in mammals, 4 of which remained undefined. Our
long-term goals are to clarify how queuine contributes to human health, raise scientific and public
awareness about its importance and exploit the newly defined pathways for therapeutic purposes.
The specific objectives of this study are to identify and characterise the unknown queuine
mechanistic enzymes and to define how queuine deficiency affects neuronal metabolism and
differentiation. Our central hypothesis is that the near universal conservation of queuine
emanates from an essential (albeit subtle) role in metabolism—through affecting ribosomal
translation—that influences differentiation and that in animals protects against age-related
neurological decline. Our rationale is based on numerous observations from the early literature,
and recent bioinformatic, biochemical, and gene-knockout studies from the Crécy and Kelly
laboratories. Our specific aims will demonstrate that; (Aim 1) queuine transport is dependent on
unique uptake receptors; (Aim 2) DUF2419 family proteins are required for queuine salvage; (Aim
3) queuine hypermodification with mannose and galactose is required for intracellular retention;
and (Aim 4) neuronal function is compromised in the absence of queuine. At conclusion the
project will have furnished the scientific community with tangible resources to interrogate
queuine’s physiological role and supply new tools for therapeutic development. The significance
of the work derives from the universality of queuine as a micronutrient for eukaryotic life with
consequences for healthy aging. The research is innovative because it, i. tackles an
unaddressed fundamental unknown of life, ii. is relevant to age-related neurological decline (a
major present-day concern) and iii. merges team expertise in bioinformatics, genetics, chemistry,
biochemistry, crystallography and metabolomics.

## Key facts

- **NIH application ID:** 10319932
- **Project number:** 5R01GM132254-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Juan D Alfonzo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,850
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319932

## Citation

> US National Institutes of Health, RePORTER application 10319932, Study of queuosine salvage and  function in eukaryotes; a forgotten micronutrient (5R01GM132254-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10319932. Licensed CC0.

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