Tuesday, July 1, 2025 7/1/2025

An LCMS-guided bioanalytical approach for rational natural product library design and optimization

Award Number: R01GM145649
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/05/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2026

Group Awards By:

View Award Description

An LCMS-guided bioanalytical approach for rational natural product library design and optimization - Project Summary/Abstract Natural products are a mainstay of drug discovery, accounting for up to 50% of approved drugs either as direct natural molecules or as inspiration for synthetic molecules. High-throughput screening of compound libraries is a common starting point for drug development campaigns. The quality of these libraries is therefore a key determinant of high-throughput screening campaign success. Natural product compound library design is particularly challenging given redundancies in natural product production between isolates and greater costs of compound production and isolation. Evidence-based and scientifically rigorous methods to optimize natural product library design are therefore urgently required. In MPIs’ previous work, they demonstrated using the example of the fungus Alternaria that liquid chromatography-tandem mass spectrometry (LC- MS/MS)-based analysis of fungal extracts could reveal the minimal number of extracts to include in a chemical library, to achieve saturation of chemical diversity. Strikingly, this number could be as small as 39 isolate extracts, depending on the Alternaria clade. It is now necessary to demonstrate the broader utility of this bioanalytical approach, to the significant biological problem of high-throughput screening natural product chemical library design. In addition, the high-throughput nature of our approach enables the systematic and unbiased assessment of different natural product diversification approaches on elicited chemical diversity. Our proposal builds on MPI’s extensive expertise in metabolomics and small molecule characterization and natural product analysis. In addition, it is enabled by the MPI’s access to the large collection of fungal isolates from the University of Oklahoma Citizen Science Soil Collection Program. This collection currently totals >78,000 isolates from 893 fungal genera. Our central hypothesis is that our untargeted metabolomics method can be applied to generate specific rules of natural product library design and provide evidence to prove or disprove current dogma governing natural product library design. We will focus on three common library design approaches, in three independent aims. Aim 1 will focus on using our approach to demonstrate that comparable chemical diversity can be obtained from focused, rationally-designed natural product libraries, compared to random serendipitous discovery. Aim 2 will systematically assess the impact of co-culture on elicited chemical diversity, comparing sympatric vs allopatric co-culture systems. Aim 3 will systematically quantify the impact of environment-mimicking culture conditions such as soil or bacterial-derived signals, on elicited chemical diversity. Overall, our results will lead to validation of a new approach for rational natural product library design, with major implications for drug development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $259,912 )
2025	2025	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Biomedical Research and Research Training	000	5	6/5/2025	NON-COMPETING CONTINUATION	$259,912
														Subtotal = $259,912

Issue Date FY: 2024 ( Subtotal = $182,469 )
2024	2024	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Biomedical Research and Research Training	002	4	6/10/2024	NON-COMPETING CONTINUATION	$265,497
2024	2023	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Biomedical Research and Research Training	004	3	8/8/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$11,242
2024	2023	UNIVERSITY OF OKLAHOMA	660 PARRINGTON OVAL RM 301	NORMAN	OK	73019	CLEVELAND	USA	Biomedical Research and Research Training	003	2	8/8/2024	NON-COMPETING CONTINUATION	-$11,242
2024	2023	UNIVERSITY OF OKLAHOMA	660 PARRINGTON OVAL RM 301	NORMAN	OK	73019	CLEVELAND	USA	Biomedical Research and Research Training	000	2	3/19/2024	NON-COMPETING CONTINUATION	-$288,308
2024	2023	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Biomedical Research and Research Training	001	3	3/20/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$205,280
														Subtotal = $182,469

Issue Date FY: 2023 ( Subtotal = $358,862 )
2023	2023	UNIVERSITY OF OKLAHOMA	660 PARRINGTON OVAL RM 301	NORMAN	OK	73019	CLEVELAND	USA	Biomedical Research and Research Training	000	2	6/8/2023	NON-COMPETING CONTINUATION	$358,862
														Subtotal = $358,862

Issue Date FY: 2022 ( Subtotal = $358,862 )
2022	2022	UNIVERSITY OF OKLAHOMA	1000 ASP AVE RM 105	NORMAN	OK	73019	CLEVELAND	USA	Biomedical Research and Research Training	000	1	9/5/2022	NEW	$358,862
														Subtotal = $358,862

Grand Total All Awards = $1,160,105

Top

All Categories

About

Search

Reports

Data Submission

Award Information

An LCMS-guided bioanalytical approach for rational natural product library design and optimization

Award Number: R01GM145649

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/05/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer