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Toward understanding the chemistry and biology of microbial DXP synthase

Award Number: R01GM143810
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: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Toward understanding the chemistry and biology of microbial DXP synthase - PROJECT SUMMARY Microbial metabolic function and adaptability are important in many facets of human health and disease. This proposal centers on studies of the microbial metabolic enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXPS). DXPS catalyzes the thiamin diphosphate (ThDP)-dependent synthesis of the essential metabolite DXP, which is found in the gut microbiota, pathogenic bacteria and parasites, but not in humans. Positioned at a metabolic branchpoint, DXP serves as a precursor to indispensable isoprenoids and vitamins, thus, we postulate DXPS plays key roles in microbiome function and microbial metabolic adaptation. Our long-term goal is to learn how microbes use DXPS in different contexts, toward understanding its roles in the microbiome and its potential as an antimicrobial target. Our group discovered a unique ligand-gated mechanism used by DXPS that bestows targets for selective inhibition and may enable DXPS to sense and respond to its environment. The goals of this proposal are to dissect how DXPS responds to molecular cues, examine this sensing mechanism in different chemical contexts, and establish novel inhibition strategies that target this distinctive feature of DXPS. Insights gained from this research will direct our thinking about DXPS function, and guide development of chemical probes needed to study DXPS roles in microbes.


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 = $0 )
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	4	8/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $398,904 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	4	6/14/2024	NON-COMPETING CONTINUATION	$398,904
														Subtotal = $398,904

Issue Date FY: 2023 ( Subtotal = $403,270 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	3	6/27/2023	NON-COMPETING CONTINUATION	$403,270
														Subtotal = $403,270

Issue Date FY: 2022 ( Subtotal = $398,904 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	2	6/9/2022	NON-COMPETING CONTINUATION	$398,904
														Subtotal = $398,904

Issue Date FY: 2021 ( Subtotal = $444,006 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	1	8/16/2021	NEW	$444,006
														Subtotal = $444,006

Grand Total All Awards = $1,645,084

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Toward understanding the chemistry and biology of microbial DXP synthase

Award Number: R01GM143810

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: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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