A novel platform for nonribosomal peptide discovery

Active Project Grant Awarded Last action

Award ID
R44GM159545
Recipient
Awarding agency
Obligated
$1,549,308

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 44% complete
Place of performance
Pittsburgh, PA 15217, USA

Award details come from USAspending.gov.

Description

Abstract
Natural products are the major source of drug molecules. Currently, 64% of small molecule drugs approved by the food and drug administration are natural products or their derivatives. Currently, the dominant technique for discovering novel natural products is bioactivity-guided isolation. However, this technique is limited to the high abundance of molecular products of microbial / plant species. Since most of the widely expressed natural products (NPS) have already been picked, bioactivity-guided techniques now lead to high rediscovery rates of known molecules. This proposal focuses on developing a novel platform for discovering natural product small molecules by integrating genome mining with computational metabolomics. With the advent of high throughput tandem mass spectrometry, metabolomics datasets collected on the supernatant of microbial / plant species have become available. However, computational techniques for identifying novel small molecules from these large and complex datasets are in their early stages. Recently, we developed dereplicator, dereplicator+, and moldiscovery to identify known small molecules by searching their tandem mass spectra against public chemical databases such as pubchem. In phase I of this proposal, we developed vinsmoc, a novel mass spectral database search method for the systematic discovery of novel variants of natural product small molecules. The overarching goal of this proposal is to develop natdiscovery, efficient and accurate methods for identifying novel non-ribosomal peptides from complex mass spectral datasets. We will further apply methods developed in this proposal to discover novel non-ribosomal peptides from 1588 actinobacterial strains. Twenty NRP with novel chemistries/enzymes will be isolated and characterized at blumberg institute, and we will screen them for antibacterial, antifungal, and antitumor activities.

Transactions

Action Obligated Date
Amendment $767,806
Original award $781,502

Quick answers

Who received award R44GM159545?

R44GM159545 was awarded to Chemia Biosciences, Inc. by National Institute of General Medical Sciences (National Institutes of Health) on July 1, 2025.

How much is award R44GM159545 worth?

$1,549,308 has been obligated on R44GM159545.

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