# Ultra-high pressure liquid chromatography coupled high resolution mass spectrometer

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $205,000

## Abstract

Abstract for parent grant:
Enzymes are powerful biocatalysts that may be repurposed for efficient and sustainable
synthesis of industrial and pharmaceutical compounds. Identifying novel enzyme-catalyzed
reactions and understanding their catalytic mechanisms is essential for expanding the
biocatalytic toolbox. We have recently discovered a unique copper-containing antibiotic, fluopsin
C, which is produced by Pseudomonas aeruginosa, a leading cause of multidrug-resistant
nosocomial infections. By studying how P. aeruginosa makes fluopsin C, we identified an
unusual biosynthetic pathway that involves novel enzyme chemistry. For instance, two iron-
dependent enzymes of a new heme-oxygenase-like enzyme family catalyze a carbon excision
and an oxidative decarboxylation and N-hydroxylation respectively. Two lyases of the
adenylosuccinate lyase enzyme family exhibit novel activities of making and breaking carbon-
sulfur bonds respectively. The chemistries we identified have expanded the catalytic capabilities
of these enzyme families. We hypothesize that the fluopsin C biosynthetic enzymes use novel
catalytic mechanisms and can be repurposed or engineered to generate new molecules. To test
this hypothesis, we will use a combination of enzyme kinetics, structural biology, spectroscopy,
and synthetic chemistry tools, with a focus on three enzymes in fluopsin C biosynthesis. Studies
of these distinct enzymes will advance the fundamental understanding of how their respective
enzyme family catalyzes diverse chemistry. Defining the mechanisms and substrate scope of
the enzymes will allow them to be further explored for biocatalytic use.

## Key facts

- **NIH application ID:** 11045816
- **Project number:** 3R01GM148685-02S2
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Bo Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,000
- **Award type:** 3
- **Project period:** 2022-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11045816

## Citation

> US National Institutes of Health, RePORTER application 11045816, Ultra-high pressure liquid chromatography coupled high resolution mass spectrometer (3R01GM148685-02S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11045816. Licensed CC0.

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