# Structural Biology of Polyether Antibiotic Biosynthesis

> **NIH NIH R01** · UNIVERSITY OF TEXAS EL PASO · 2020 · $151,000

## Abstract

The overarching goal of our research program is to elucidate how nature produces polyether
natural products. Polyethers are a subgroup of polyketide natural products and, as a class, they
possess a wide range of useful activities, including antibacterial, antifungal, and anticancer
properties. However, polyether drug development is hampered by our inability to quickly and
efficiently synthesize natural polyethers and their derivatives for medicinal chemistry and drug
optimization studies. This is due to the unusually complex structure of natural polyethers. An
attractive solution to this problem is to biosynthesize complex polyethers using engineered
laboratory-friendly organisms such as bacteria or yeast. This approach is expected to make
countless new polyethers accessible for drug research. In order to create a robust and reliable
polyether bioproduction platform, we must first achieve a detailed and comprehensive
understanding of how polyethers are produced in living organisms. More than 100 different
polyether natural products have been discovered so far, and examination of known polyether
biosynthetic gene clusters show that all polyethers are generated via a common three-stage
biosynthetic scheme. Stage 1: construction of the polyketide backbone by modular polyketide
synthases. Stage 2: stereoselective epoxidation of the polyene intermediate by a monooxygenase.
Stage 3: formation of the hallmark cyclic ether groups by one or more epoxide hydrolases. The
universal nature of this scheme ensures that investigation of any one particular polyether
biosynthesis pathway and its associated enzymes will lead to a general understanding of how
nature generates polyethers. In this project, we will study the biosynthetic enzymes from the
lasalocid A biosynthesis pathway from Streptomyces lasaliensis. Lasalocid A biosynthesis
pathway is an excellent model system for studying how nature produces polyethers because it
consists of just nine enzymes, yet it possesses all the hallmark chemical transformations of
polyether biosynthesis.

## Key facts

- **NIH application ID:** 10036330
- **Project number:** 1R01GM138990-01
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Chu-Young Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $151,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10036330

## Citation

> US National Institutes of Health, RePORTER application 10036330, Structural Biology of Polyether Antibiotic Biosynthesis (1R01GM138990-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10036330. Licensed CC0.

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