R44GM159545

A novel platform for nonribosomal peptide discovery - project summary.

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.

Chemia Biosciences

THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES (NIGMS) SUPPORTS BASIC RESEARCH THAT INCREASES OUR UNDERSTANDING OF BIOLOGICAL PROCESSES AND LAYS THE FOUNDATION FOR ADVANCES IN DISEASE DIAGNOSIS, TREATMENT, AND PREVENTION. NIGMS ALSO SUPPORTS RESEARCH IN SPECIFIC CLINICAL AREAS THAT AFFECT MULTIPLE ORGAN SYSTEMS: ANESTHESIOLOGY AND PERI-OPERATIVE PAIN, CLINICAL PHARMACOLOGY ?COMMON TO MULTIPLE DRUGS AND TREATMENTS, AND INJURY, CRITICAL ILLNESS, SEPSIS, AND WOUND HEALING.? NIGMS-FUNDED SCIENTISTS INVESTIGATE HOW LIVING SYSTEMS WORK AT A RANGE OF LEVELSFROM MOLECULES AND CELLS TO TISSUES AND ORGANSIN RESEARCH ORGANISMS, HUMANS, AND POPULATIONS. ADDITIONALLY, TO ENSURE THE VITALITY AND CONTINUED PRODUCTIVITY OF THE RESEARCH ENTERPRISE, NIGMS PROVIDES LEADERSHIP IN SUPPORTING THE TRAINING OF THE NEXT GENERATION OF SCIENTISTS, ENHANCING THE DIVERSITY OF THE SCIENTIFIC WORKFORCE, AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

National Institute of General Medical Sciences (NIGMS) [HHS - NIH]

Pennsylvania United States

State-Wide

PHS 2024-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) (PA-24-245)