# Synthetic biology approaches to new fluorinated pharmaceuticals

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $293,983

## Abstract

Project Summary/Abstract
Fluorinated pharmaceuticals represent a rapidly expanding class of small molecule drugs that
have become important in the treatment of diverse human health conditions ranging from
cancer to high cholesterol. Indeed, the selective introduction of fluorine into compounds has
become a key strategy for chemists to rationally tune the behavior of small molecules in order to
turn a lead compounds into an effective treatment. Indeed, ~30% of pharmaceuticals now
contain fluorine, including three of the top five-selling drugs. However, these same chemical
properties limit our ability to specifically incorporate fluorine into molecules and consequently
our ability to fully exploit the potential that fluorine provides as a design element in the pipeline
of drug design and discovery. New developments in synthetic chemical methods have greatly
improved our ability to make carbon-fluorine bonds, but challenges in the synthesis and
preparation of organofluorine compounds continue to restrict the scope of molecular structures
and methods that can be used to screen for new drug candidates. Our group has been
developing alternative synthetic biology approaches to engineer enzymatic and living systems
for the production of complex fluorinated compounds with bioactivity, with the long-term goal of
developing new approaches to fluorinated drug discovery. Specific aims of this proposal include:
(i) elucidating the molecular mechanism of naturally-occurring fluorine selectivity in enzymes
from Streptomyces cattleya, one of the few known native organofluorine-producing organisms,
in order to build a knowledgebase for engineering fluorine-selective enzymes, (ii) studying the
mechanism of fluorinated extender unit usage in polyketide synthases, which produce a large
family of medicinally-important natural products, and (iii) developing in vitro and in vivo methods
for production of fluorinated natural products in the polyketide family.

## Key facts

- **NIH application ID:** 9880436
- **Project number:** 5R01GM123181-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** MICHELLE C CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,983
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880436

## Citation

> US National Institutes of Health, RePORTER application 9880436, Synthetic biology approaches to new fluorinated pharmaceuticals (5R01GM123181-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9880436. Licensed CC0.

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