# Discovery and Application of New Halogenases

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $58,930

## 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:** 10581996
- **Project number:** 3R01GM134271-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** MICHELLE C CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $58,930
- **Award type:** 3
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10581996

## Citation

> US National Institutes of Health, RePORTER application 10581996, Discovery and Application of New Halogenases (3R01GM134271-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10581996. Licensed CC0.

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