# Abiological Enzymatic C–H Functionalization for Bioactive Molecule Construction and Diversification

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2021 · $24,778

## Abstract

Project Abstract (parent award R01GM138740: Abiological Enzymatic C–H Functionalization for Bioactive
Molecule Construction and Diversification)
Advances in molecule construction and diversification expedite drug discovery and development. Given the
ubiquity of C–H bonds in molecules, methods to selectively convert them into functional groups represent one of
the most attractive strategies to introduce diversity efficiently and enable rapid molecular construction. Despite
significant advances, however, directly and selectively functionalizing complex molecules bearing multiple
stereocenters and delicate functional groups remains a major challenge. Creative use of enzymes to perform
new-to-nature C–H functionalization reactions can greatly accelerate such processes, while providing
sustainable and more selective alternatives to currently used stoichiometric methods or noble metal catalysts.
We propose to start from enzymes that derivatize complex bioactive molecules via C–H hydroxylation and
engineer them by directed evolution to perform abiological C–H unctionalization to furnish new C–C bonds or
C–N bonds. We envision that these efforts will establish a versatile biocatalytic platform that will provide rapid
access to derivatives of complex molecules with selectivity and efficiency unattainable by current synthetic
approaches. This work will also illustrate evolutionary innovation mechanisms and the rapid acquisition of novel
genetically encoded functions.

## Key facts

- **NIH application ID:** 10386710
- **Project number:** 3R01GM138740-02S2
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** FRANCES H ARNOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $24,778
- **Award type:** 3
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386710

## Citation

> US National Institutes of Health, RePORTER application 10386710, Abiological Enzymatic C–H Functionalization for Bioactive Molecule Construction and Diversification (3R01GM138740-02S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10386710. Licensed CC0.

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