Identification and biosynthesis of dehydrated nonribosomal peptides from streptomyces
Ended Project Grant Awarded Last action
- Award ID
- F32GM154449
- Recipient
-
University Of North Carolina At Chapel Hill UEI D3LHU66KBLD5
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $300,892
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date
- Place of performance
- Chapel Hill, NC 27599, USA
Award details come from USAspending.gov.
Description
- Abstract
- Nonribosomal peptides are an important class of natural products which display great structural and functional diversity. As many nonribosomal peptides act as antimicrobials, the identification of novel bioactive nrps can lead to the development of new therapeutics for the treatment of antimicrobial resistant microorganisms. Dehydrated nonribosomal peptides, peptides derived from or containing one or more a, SS-dehydroamino acids (dhaas), are key targets for further therapeutic development due to their structural rigidity, resistance to proteolytic degradation, and enhanced chemical reactivity. The LI lab has focused on a specific class of dehydrated nonribosomal peptides whose biosynthesis stems from biosynthetic gene clusters (bgcs) containing nonribosomal-peptide synthetases (nrpss) with c domains which modify amino acids (cmodaa). We have recently characterized a class of these cmodaa domains which dehydrates SS-hydroxy amino acids to dhaas in nonribosomal peptide biosynthesis, and work from our lab and others has demonstrated that these cmodaaderived nonribosomal peptides display a diverse array of bioactivities. However, the identity of many cmodaa derived nonribosomal peptides is undiscovered, and their biosynthetic pathways and biological roles remain uncharacterized. Through genome mining we have identified nearly 4,500 nonidentical cmodaa domains, many of which are distributed among soil bacteria including streptomyces. The research described herein is aimed to elucidate the unknown products of several of these bgcs from streptomyces and characterize the role of the cmodaa domain in their biosynthesis. I will use a combination of in silico analysis of the biosynthetic gene clusters, comparative metabolomics, genetic manipulation, and NMR analysis to elucidate the cryptic products of these bgcs. Once the nonribosomal peptide structure has been determined, i will perform a battery of in vitro enzyme assays to elucidate the core enzymes involved in nonribosomal peptide biosynthesis, and the biosynthetic role of the cmodaa domains within each BGC. Completion of the proposed research will lead to the discovery of novel cmodaa derived dhaa nonribosomal peptides with potential therapeutic applications. Furthermore, the findings of this research will provide a base of knowledge that will extend to the discovery of other cmodaa containing bgcs and characterization of their dhaa containing products.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $78,040 | |
| Amendment | $74,284 | |
| Amendment | $0 | |
| Amendment | $74,284 | |
| Amendment | $0 | |
| Original award | $74,284 |
Quick answers
Who received award F32GM154449?
F32GM154449 was awarded to University Of North Carolina At Chapel Hill by National Institute of General Medical Sciences (National Institutes of Health) on December 1, 2024.
How much is award F32GM154449 worth?
$300,892 has been obligated on F32GM154449.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award