# Integrative Multidisciplinary Discovery Platform to Unlock Marine Natural Products Therapeutic Opportunities

> **NIH NIH RM1** · UNIVERSITY OF FLORIDA · 2022 · $1,786,979

## Abstract

PROJECT SUMMARY
We have assembled an entirely Florida-centric collaborative research team with collective expertise in microbial
natural products chemistry and pharmacology, genomics, bacterial enzymology, bioinformatics, synthetic
biology, chemical synthesis, and cyanobacterial and sponge chemical ecology and phylogenetics. The team is
complemented by an out-of-state expert in metagenomics and bioinformatics integration. This geographical
cluster of expertise being in the state with the greatest marine biodiversity in the continental US provides a dual
benefit and unique opportunity to explore systems that are likely to hold some of the most promise in terms of
biosynthetic potential: marine cyanobacterial communities, consisting of benthic filamentous cyanobacteria that
are associated with unique microbial diversity, and sponges and their associated rich and unique microbiome in
a local hotspot of biodiversity. Compounds produced by these communities are known to cover therapeutically
relevant chemical space and are therefore suited as starting points for drug discovery. In a targeted fashion, we
will obtain high quality (meta)genome and (meta)transcriptome sequence information from sponge-associated
microbiomes and cyanobacteria using state-of-the-art sequencing techniques. We will build an integrated, multi-
component platform that leverages existing bioinformatics tools and newly developed artificial intelligence-based
tools to shine new light at their genomes with the goal of identifying novel biosynthetic gene clusters, particularly
those unattainable with current tools, and even chemical skeletons. We will express natural products encoded
by the clusters by employing five types of complementary synthetic biology systems that we have strategically
developed over the past several years. These systems originating from five bacterial phyla commonly associated
with both marine cyanobacterial and sponge samples cover diverse genetic backgrounds and are expected to
effectively translate the identified genetic information of a variety of organisms into chemicals with proper system
optimization. We will evaluate and analyze metabolites and expression profiles using LC-MS-based
metabolomics and NMR and characterize associated new enzymology. Natural products derived from chemical
extract and fraction libraries and those generated through our expression systems or chemical synthesis will be
tested in our multidimensional screening platform, consisting of unbiased phenotypic assays in various in vitro
and in vivo models as well as experimental and computational target-based functional assays. This approach
will enable us to capture a broad array of activities from expressed and unexpressed genes. Selected bioactive
natural products will be scaled by chemical synthesis, and bioprobes and enzyme substrates will be prepared
for in-depth biological studies and enzymology research, respectively. Successful completion of these aims by
our established multi...

## Key facts

- **NIH application ID:** 10413304
- **Project number:** 1RM1GM145426-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Mohamed Abou Donia
- **Activity code:** RM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,786,979
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413304

## Citation

> US National Institutes of Health, RePORTER application 10413304, Integrative Multidisciplinary Discovery Platform to Unlock Marine Natural Products Therapeutic Opportunities (1RM1GM145426-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10413304. Licensed CC0.

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