# Discovery and application of new halogenases

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $313,984

## Abstract

Project Summary/Abstract
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, which remains challenging to achieve. 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, and (iii)
developing applications for halogenases to produce new amino-acid based products.

## Key facts

- **NIH application ID:** 10126030
- **Project number:** 5R01GM134271-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** MICHELLE C CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,984
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126030

## Citation

> US National Institutes of Health, RePORTER application 10126030, Discovery and application of new halogenases (5R01GM134271-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10126030. Licensed CC0.

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