# Abiological enzymatic C-H functionalization for bioactive molecule construction and diversification

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2021 · $322,423

## Abstract

Project Abstract
 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 functionalization 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:** 10207693
- **Project number:** 5R01GM138740-02
- **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:** $322,423
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207693

## Citation

> US National Institutes of Health, RePORTER application 10207693, Abiological enzymatic C-H functionalization for bioactive molecule construction and diversification (5R01GM138740-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10207693. Licensed CC0.

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