# Genetic analyses of molybdenum cofactor biology

> **NIH NIH R35** · SANFORD RESEARCH/USD · 2022 · $415,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Molybdenum cofactor (Moco) is a 520-dalton prosthetic group that is required for animal life. Moco was present
in the last universal common ancestor and its synthesis persists in all domains of life. Loss-of-function mutations
in the genes encoding Moco-biosynthetic enzymes cause human Moco deficiency, a rare and lethal inborn error
of metabolism. In animals, Moco supports the activity of 4 enzymes including sulfite oxidase and xanthine
dehydrogenase. These enzymes catalyze critical steps in the metabolism of sulfur amino acids and purines
respectively, essential pathways that cause disease when perturbed. Thus, understanding Moco biology and the
far-reaching metabolic consequences of Moco deficiency is an important goal of human health. The long-term
goal of my research is to i) discover new mechanisms employed by animals to maintain Moco homeostasis and
ii) identify and characterize genetic pathways that regulate Moco-mediated metabolism. We employ an
interdisciplinary approach using unbiased genetic strategies in the model organism Caenorhabditis elegans in
combination with functional genomics, biochemistry, and cellular biology to explore previously intractable areas
of Moco biology. This proposal builds on our recent discovery that dietary Moco is bioavailable to C. elegans.
Our work reveals a previously unimagined pathway for Moco transport in an animal. The first goal of the current
proposal is to define the network of proteins necessary for the stable uptake and distribution of Moco in C.
elegans. The second goal of this proposal is to identify regulatory pathways that control sulfur amino acid and
purine metabolism; essential metabolic pathways governed by Moco-requiring enzymes. The proposed research
program will define fundamental pathways that govern Moco biology and may suggest new therapeutic strategies
to treat rare and common diseases where Moco and Moco-mediated metabolism are disturbed.

## Key facts

- **NIH application ID:** 10499645
- **Project number:** 1R35GM146871-01
- **Recipient organization:** SANFORD RESEARCH/USD
- **Principal Investigator:** Kurt Warnhoff
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $415,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499645

## Citation

> US National Institutes of Health, RePORTER application 10499645, Genetic analyses of molybdenum cofactor biology (1R35GM146871-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499645. Licensed CC0.

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