# Genomics-Accelerated Discovery and Biosynthesis of Phosphonic Acid Natural Products

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $305,183

## Abstract

PROJECT SUMMARY
Microbial phosphonic acids are a class of understudied natural products with significant utility in medicine. The
antimicrobial, antiviral, and antimalarial activity of many useful phosphonic acids derives from potent and
specific inhibition of metabolic enzymes through chemical mimicry of their natural substrates. These properties,
along with the trove of novel biosynthetic gene clusters encoded within microbial genomic datasets, highlight
their potential of phosphonic acid natural products new antimicrobials. In this project we focus our efforts on
realizing their genomic potential of these compounds by establishing fundamental genetic and biochemical
principles that define their biosynthetic and bioactivity landscape. Filling these gaps in knowledge will provide a
systems-level understanding of natural product biosynthesis necessary to improve discovery and engineering
of new phosphonic acids. Specifically, we investigate three recently discovered phosphonic acid peptides to
uncover unusual hydroxylation, reduction, amination, and amino acid ligation enzymes, and the molecular
basis of their antimicrobial activity. We expand and refine the framework for phosphonic acid natural product
genomics through the isolation of new compounds from cryptic gene clusters, discovery of new pathways and
enzymes for C-P bond formation, and the development of a classification scheme to improve prediction of
phosphonic acid gene clusters and their chemical products.

## Key facts

- **NIH application ID:** 10449297
- **Project number:** 5R01GM137135-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Kou-San Ju
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $305,183
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449297

## Citation

> US National Institutes of Health, RePORTER application 10449297, Genomics-Accelerated Discovery and Biosynthesis of Phosphonic Acid Natural Products (5R01GM137135-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10449297. Licensed CC0.

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