# Development of Selective Oxidative Biocatalytic Methods

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $24,651

## Abstract

Project Summary
The ability to access complex target molecules with sustainable methodology is imperative to the development
of novel drugs, which will be necessary to treat antimicrobial resistance and emerging infectious diseases.1 Site-
selective oxidation reactions are fundamental to the current synthetic logic towards complex scaffolds and the
decoration of these cores, which is key to the development of novel drugs.2,3 Nature can use enzymes to impart
exquisite site-selectivity in oxidations based on the three-dimensional control exerted by the active site while
bringing a substrate and oxidant together. Taking inspiration from Nature, I plan to utilize flavin-dependent
monooxygenases to site-selectively oxidize a variety of non-native arenes and heteroarenes substrates (Aim 1),
which will allow access to novel building blocks, pharmaceuticals, and natural products and their derivatives.
The sequence space of flavin-dependent monooxygenases is vast, therefore, logically picking biocatalysts that
have improved, site-selectivity, yield, or substrate scope, requires a strategy. I plan to use sequence similarity
networks, (to visualize how similar sequences are), sequence alignments, (to probe amino acid changes
proximal to active sites), three-dimensional active site analysis, (to identify key amino acids and size of active
site), and docking studies, (to understand how a substrate interacts with an active site) (Aim 2). These techniques
can be used together to explain and predict trends in substrate scope, and site-selectivity. Ultimately, these
techniques will help me to logically choose biocatalysts that have improved properties such as expanded
substrate scope, divergent site-selectivity, or improved yield to strengthen the proposed oxidative method
development.
Together these aims will develop site-selective biocatalytic oxidation methods applicable to a variety of arene
and heteroarene substrates. This research will broadly impact biocatalysis investigations by developing a high
throughput platform for nonnative substrate screening across a family of enzymes, and informing what tools are
important for rationally choosing existing biocatalysts. Finally, the proposed site-selective oxidative method will
improve the ease and efficiency of synthesis and derivatization of molecules that are important to human health.

## Key facts

- **NIH application ID:** 10760241
- **Project number:** 5F31GM147942-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sarah Elizabeth Champagne
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $24,651
- **Award type:** 5
- **Project period:** 2023-01-01 → 2024-06-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10760241

## Citation

> US National Institutes of Health, RePORTER application 10760241, Development of Selective Oxidative Biocatalytic Methods (5F31GM147942-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10760241. Licensed CC0.

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