# Biosynthesis and Enzymology of Antifungal Natural Products

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $616,076

## Abstract

ABSTRACT
 The combination of high frequencies of infection, high mortality rates, emergence of drug resistance,
small number of therapeutic options and a depleted discovery pipeline has resulted in an urgent need for finding
new antifungal molecules. Natural products, especially those produced by fungal species as natural antifungal
weapons, have been and will continue to play important roles and provide leads for drug discovery. Realizing
the immense potential of natural products as antifungal leads, and the prospects of discovering new structures
through genome-guided methods, we are proposing a comprehensive and multidisciplinary project to investigate
the biosynthesis of fungal-derived 2-pyridone alkaloids, which are complex natural products with potent and
selective antifungal activities. We will be particularly focused on a diverse set of enzyme-catalyzed pericyclic
reactions that give rise to the polycyclic scaffold important for biological activity. Uncovering these enzymes,
followed by detailed investigation of the mechanisms and sequence-activity relationships, will improve our
fundamental understanding of enzyme catalysis, and enable biosynthetic engineering approaches to generate
natural product analogs, and expand genome mining leads for new antifungals. This multi-PI proposal bring
together complementary expertise in three aspects of natural product research: biosynthesis, computational
chemistry and synthesis. Together we will address three aims: 1) Investigate SAM-dependent pericyclase using
leporin as a model system. 2) Investigate Alder-Ene and dephenylation reactions in pyridoxatin biosynthesis;
and 3) Investigate biosynthesis of decalin-containing antifungal 2-pyridone compounds. Insights into the
biosynthesis of these molecules will reveal fundamental insights into enzymes that catalyze pericyclic reactions,
and provide leads for structure-guided natural product discovery.

## Key facts

- **NIH application ID:** 9823853
- **Project number:** 5R01AI141481-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Neil K. Garg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $616,076
- **Award type:** 5
- **Project period:** 2018-11-15 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823853

## Citation

> US National Institutes of Health, RePORTER application 9823853, Biosynthesis and Enzymology of Antifungal Natural Products (5R01AI141481-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9823853. Licensed CC0.

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