# Expanding the chemistry of life: New enzymatic platforms for synthesis of bioactive organofluorines

> **NIH NIH R00** · JOHNS HOPKINS UNIVERSITY · 2021 · $249,000

## Abstract

Project Summary/Abstract
Enzymes are well known for catalyzing chemical transformations with exquisite specificity and selectivity under
environmentally benign conditions. Thus, there is a continuing need for the development of new enzymes that
can effect critical synthetic transformations. One important type of transformations that is rarely present in current
catalytic repertoire of biology is reactions for synthesis of organofluorine compounds. Organofluorine molecules
have assumed a privileged position in modern pharmaceutical industry, which comprise ~ 30% of all
pharmaceuticals and ~ 60% of all FDA-approved radiotracers for positron emission tomography (PET). The focus
of this proposal is to generate new enzymatic platforms for the synthesis of organofluorine molecules. With
protein engineering techniques like directed evolution, we will bring fluorination activities into existing proteins
that share mechanistic features with synthetic fluorination reactions. These enzymatic platforms will expand the
chemical space of biosynthesis tremendously and open up possibilities to develop whole new biosynthetic
pathways for organofluorine synthesis. On their own, the enzymes developed would lead to highly efficient and
selective synthetic routes to organofluorines that are currently unobtainable or feasible at scale. The structural
and kinetic investigations of these new enzymes will greatly extend our understanding of enzymology and
biochemistry to catalytic reactions unprecedented in nature. These new fluorination enzymes could be
genetically incorporated into living hosts and coupled with existing biosynthetic pathways, enabling specific
incorporation of fluorine groups into complex bioactive molecules. These research efforts will empower the
development of new fluorine-based therapeutics and provide a paradigm for bringing non-biological chemistries
to life.

## Key facts

- **NIH application ID:** 10065508
- **Project number:** 5R00GM129419-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xiongyi Huang
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065508

## Citation

> US National Institutes of Health, RePORTER application 10065508, Expanding the chemistry of life: New enzymatic platforms for synthesis of bioactive organofluorines (5R00GM129419-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10065508. Licensed CC0.

---

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