# A Biosynthetic Strategy to Manufacture Less Toxic Amphotericins

> **NIH NIH F32** · NORTHWESTERN UNIVERSITY · 2022 · $24,519

## Abstract

PROJECT ABSTRACT
Amphotericin B is a powerful antifungal treatment however, widespread use is prevented by dose limiting toxicity.
Nontoxic analogs have been discovered but their structural complexity precludes a practical chemical synthesis
on industrial scale. Microbes are extraordinarily adept at producing amphotericin, as metric tons are fermented
annually. Enzymes found within amphotericin’s natural biosynthetic pathway can serve as exceptionally specific
and renewable biocatalysts that can overcome many common limitations encountered during its chemical
synthesis. Reimagining aspects of amphotericin’s biosynthesis could therefore produce a robust and sustainable
path to these nontoxic variants. This proposal aims to develop a deep understanding of several catalytic
processes involved in amphotericin’s natural biosynthesis. Harnessing this knowledge, key enzymes and
biosynthetic pathways will be evolved and engineered to construct a biosynthetic strategy to manufacture less
toxic amphotericins. Cell-free protein synthesis provides a means to prototype these enzymes and pathways in
a quantitative and high-throughput manner. Ultimately this work is expected to be an efficient platform to create
new, best-in-class antifungal candidates, provide probes to interrogate structure-activity relationships dictating
AmB’s potency and toxicity, and drive the continued development of enzymes as renewable, ecologically-safe
and flexible biocatalysts for pharmaceutical sciences. The proposal provides ample opportunities for me to build
on the knowledge from my undergraduate and graduate studies so I may continue to learn, innovate, and develop
skills to be a well-rounded scientific leader. Based on the unique scientific expertise and mentoring track record
of my Sponsor and Cosponsor, they are the ideal pair to provide constructive guidance in science and career
development, and maximize my potential to drive this project towards success.

## Key facts

- **NIH application ID:** 10383158
- **Project number:** 5F32GM142211-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jonathan Webb Bogart
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $24,519
- **Award type:** 5
- **Project period:** 2021-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10383158

## Citation

> US National Institutes of Health, RePORTER application 10383158, A Biosynthetic Strategy to Manufacture Less Toxic Amphotericins (5F32GM142211-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10383158. Licensed CC0.

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