# Discovery and Application of New Halogenases

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $64,564

## Abstract

Project Summary
 The rapid and modular generation of molecular diversity is key to the search for new chemical
functions. One particularly useful functional group is the halogen (X = Cl, Br, I), which enables many
selective and effective downstream strategies for creating structural complexity. In this regard, halogenase
enzymes have provided an important and complementary approach to synthetic catalysts for regio- and
stereoselective introduction of a halogen substituent on a complex scaffold. While many families of
halogenases exist, the radical halogenases provide the greatest potential for reaction diversity, as they are
competent to replace unactivated C-H bonds with a halogen unlike those that operate by electrophilic or
nucleophilic mechanisms. However, the substrate scope of these enzymes has been limited to date to either
protein-bound substrates or large late-stage natural product intermediates. Our group has discovered a new
clade of radical halogenases capable of reacting with small molecule substrates. We now seek to take
advantage of this discovery to develop new tools for in vitro and in vivo synthesis. Specific aims of this
proposal include: (i) elucidating the structure and mechanism of these new radical halogenases, which will
provide important insight into their engineering, (ii) investigating and engineering selectivity in
halogenases.

## Key facts

- **NIH application ID:** 10798668
- **Project number:** 3R01GM134271-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** MICHELLE C CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $64,564
- **Award type:** 3
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798668

## Citation

> US National Institutes of Health, RePORTER application 10798668, Discovery and Application of New Halogenases (3R01GM134271-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10798668. Licensed CC0.

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