# Biosynthesis of antifungal nucleoside antibiotics

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $159,212

## Abstract

Project Summary/Abstract
This equipment supplement project aims to purchase a liquid chromatography coupled mass spectrometry
(LCMS) instrument essential for the discovery, biosynthesis, and development of antifungal nucleoside
antibiotics. The parent R01 aims to understand the biosynthesis of peptidyl nucleoside (PN) antifungal antibiotics
active against multiple pathogenic fungi such as the causal agent of "Valley Fever" and to discover novel
antifungal agents using this knowledge. For this study, one of the most significant technical challenges is the
characterization of hydrophilic nucleoside compounds because these compounds do not bind to the conventional
reverse-phase columns most frequently used for LCMS. To overcome this challenge, we propose the purchase
of a biocompatible (metal-free) ultra-high-performance liquid chromatography (UHPLC) unit coupled with a
quadrupole time of flight (QTOF) MS device. Biocompatible UHPLC will allow the use of various hydrophilic
interaction chromatography (HILIC) columns for the analysis of polar metabolites. The QTOF MS detector will
allow discovery-oriented (untargeted) analyses of complex metabolite mixtures. The proposed system will enable
the purification of the analytes while monitoring MS chromatograms, which is impossible with other LCMS
instruments available at Duke. Also, having an instrument dedicated to the preparation and analysis of
hydrophilic compounds will significantly improve the turnaround time of our analyses from 2-3 weeks to within a
day. Therefore, the purchase of the proposed LCMS will provide unique capabilities currently unavailable to us
but essential for the successful characterization of nucleoside antibiotics proposed in the parent project. The
proposed research is significant because it will provide a basis for the future chemoenzymatic preparation or
genome mining discovery of novel nucleoside antifungals.

## Key facts

- **NIH application ID:** 10389266
- **Project number:** 3R01GM115729-06S2
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kenichi Yokoyama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $159,212
- **Award type:** 3
- **Project period:** 2015-07-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389266

## Citation

> US National Institutes of Health, RePORTER application 10389266, Biosynthesis of antifungal nucleoside antibiotics (3R01GM115729-06S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10389266. Licensed CC0.

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