# Mechanisms of unusual enzymes in the biosynthesis of a copper-containing antibiotic

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $306,670

## Abstract

Abstract
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:** 10567957
- **Project number:** 1R01GM148685-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Bo Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $306,670
- **Award type:** 1
- **Project period:** 2022-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10567957

## Citation

> US National Institutes of Health, RePORTER application 10567957, Mechanisms of unusual enzymes in the biosynthesis of a copper-containing antibiotic (1R01GM148685-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10567957. Licensed CC0.

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