# Deciphering microbial metalloenzyme functions in microaerobic host environments

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2024 · $373,652

## Abstract

Project Summary
Commensal and pathogenic bacteria inhabit various oxygen-depleted niches in the human body, such as the
gastrointestinal tract, wound tissue, and the lung mucosa. Adaptation to these environments requires distinct
anaerobic biochemistry to support colonization and survival. An understanding of these biochemical strategies
could present unique opportunities to develop novel therapeutics that overcome challenges of antibiotic
resistance and bacterial persistence. However, we lack fundamental knowledge of the diverse chemistry that
microbes use in anaerobic and microaerobic environments. The proposed studies outline our approach to
elucidate the molecular mechanisms, biochemical reactions, and biological roles of metalloenzymes in host-
microbe interactions. Metalloenzymes play central roles in cellular redox chemistry. Whereas classes of
metalloenzymes that active oxygen for redox reactions have been studied for decades, metalloenzyme families
that function in the absence of oxygen remain poorly characterized. In this project, we interrogate the chemical
and biological functions of a newly discovered family of metalloenzyme oxidases that are prevalent in bacterial
pathogens and human gut microbes. The few known representatives of this family catalyze oxygen-independent
hydroxylation reactions in key cellular processes, including cofactor biosynthesis and RNA modification. We will
use these known enzymes to establish the requirements for catalysis and to discern their postulated roles in
microoxic conditions. Beyond the members with established functions, emerging metalloenzyme families also
represent an untapped source of biochemical diversity. We will leverage genomics and protein bioinformatics to
discover new enzymatic chemistry within this poorly characterized superfamily. The proposed work will reveal
previously unknown redox chemistry, establish biochemical responses to microaerobic conditions, and set the
stage to interrogate the importance of these reactions in host-microbe interactions. The ultimate goal of this
research program is to gain a molecular understanding of microbial adaptation to O2 limitation that can be
leveraged to treat elusive drug-resistant bacterial pathogens.

## Key facts

- **NIH application ID:** 10888245
- **Project number:** 5R35GM150913-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Lauren Julia Rajakovich
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,652
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888245

## Citation

> US National Institutes of Health, RePORTER application 10888245, Deciphering microbial metalloenzyme functions in microaerobic host environments (5R35GM150913-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10888245. Licensed CC0.

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