# A Chemo-Mimetic Platform to Reprogram Metalloenzymes for Non-Natural Biocatalytic C-H Functionalization Reactions

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2022 · $309,629

## Abstract

Abstract/Summary
The development of methods for molecule construction and functionalization has expedited the drug
development process during the past decades. To this end, enzymatic C–H functionalization represents a
powerful approach to enable rapid molecular construction. Harnessing the ubiquitous C–H bonds in organic
molecules and genetic tunability of protein catalysts, enzymatic C–H functionalization provides sustainable
strategies to effect chemical transformations with high selectivity and efficiency. Despite significant advances,
the reaction scope of current enzymatic C–H functionalization is restricted to chemical reactivities acquired
through natural evolution. This limitation hampers the applications of enzymes for drug development as many
medicinally important chemical motifs are rarely present or even completely absent in biology. To expand the
chemical space of biosynthesis, we herein aim to develop new biocatalytic systems by repurposing
metalloenzymes for C–H functionalization reactions currently not present in biology. By integrating protein
engineering, computational modeling, organic synthesis, and biochemical and inorganic spectroscopic
analysis, we will create collections of metalloenzyme catalysts that can directly functionalize inert C(sp3)–H
bonds to install biomedically relevant chemical moieties. We envision that the enzymes we create will not
only provide powerful genetically encoded tools for numerous synthetic and biological applications, but will
also offer a fertile ground to enrich our fundamental knowledge of biochemistry and enzymatic catalysis

## Key facts

- **NIH application ID:** 10501566
- **Project number:** 1R35GM147639-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xiongyi Huang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $309,629
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501566

## Citation

> US National Institutes of Health, RePORTER application 10501566, A Chemo-Mimetic Platform to Reprogram Metalloenzymes for Non-Natural Biocatalytic C-H Functionalization Reactions (1R35GM147639-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10501566. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*