# Mapping and Understanding Production of Natural Products in Fungi

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $517,365

## Abstract

Project Summary/Abstract
 The goal of this project is to improve a genome-driven, correlation-based platform to unearth and produce
new bioactive compounds from fungi. This platform and research will deliver access to a large repertoire of fungal
natural products (NPs), which historically have been a great source of new medicines and useful compounds.
Typical estimates have NPs and their derivatives accounting for ca. 75% of currently used antibiotics and nearly
60% of anti-cancer drugs along with numerous antiviral, antiparasitic, antifungal, and immunosuppressive
medicines. Despite their historical successes, traditional screening programs have been severely curtailed due
to declining numbers of promising new candidates and lack of ready access to new compounds. At the same
time, analysis of over one thousand fungal genomes suggests that tens of thousands of high-value NPs have
yet to be identified and screened. Thus, new technologies are needed and here we describe an integrated plan
to systematically tap into this vast potential of fungal metabolites through genomics, metabolomics, bioactivity
screening and molecular biology. In the previous funding period, we developed an untargeted approach called
`metabologenomics' that correlates genomic content with metabolite output to uncover hundreds of new NPs
and their gene clusters from soil actinobacteria. In this competing renewal, we now propose to extend the method
to 300 fungi while integrating bioactivity screening in Aim 1. Activities described in this proposal will reduce
technical barriers by establishing new workflows, improving experimental methodology, and refining scoring
metrics to create a discovery platform with the ability to help unlock the medicinal potential of NPs in the fungal
kingdom. In Aim 2, we focus on the targeted capture and expression of BGCs in specific euchromatic loci in a
widely used host for NP heterologous expression, Aspergillus nidulans. The two Aims of the project describe the
generation of genomic, metabolomics, bioactivity, and expression data. We further propose to make data- and
milestone-driven progress on the combination of these complementary data types to systematically examine a
set of 300 fungal strains. With a proven track record of deep collaboration among the team members involved,
we will deliver a robust implementation of the proposed activities to provide a well-defined path to discovery of
bioactive NP/BGC pairs, and study the production of new molecules from diverse fungi.

## Key facts

- **NIH application ID:** 10840987
- **Project number:** 5R01AT009143-20
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** NEIL L KELLEHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $517,365
- **Award type:** 5
- **Project period:** 2016-04-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840987

## Citation

> US National Institutes of Health, RePORTER application 10840987, Mapping and Understanding Production of Natural Products in Fungi (5R01AT009143-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10840987. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*