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Biosynthesis and Reactivity of the Active Site of the FeFe Hydrogenases

Award Number: R01GM061153
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: 07/01/2000
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Biosynthesis and Reactivity of the Active Site of the FeFe Hydrogenases - Project Summary Hydrogenase enzymes are pervasive, being found in bacteria, archaea, and some higher organisms. These enzymes are hosted by some pathogens, often in anaerobic environments including the human gut. The hydrogenases mediate the most fundamental chemical reaction: the interconversion of H2 with protons and reducing equivalents. The enzymes are structurally exceptional with an array of distinctive cofactors, especially the site of H2 binding and release. Interest in such enzymes stems from three angles: the possibility that some pathogens could be controlled rationally, the excitement about their unusual structures, and the commercial implications of hydrogen production/oxidation in the context of fuel cells. Two major classes of hydrogenases exist, [NiFe]- and [FeFe]-hydrogenases. This project is almost exclusively focused on the latter. More specifically, this project aims to elucidate the biosynthesis of the active site of [FeFe] enzymes, the faster hydrogenase and the one most amenable to development for other applications. This project is timely because we have just defined the sequence by which the three maturase enzymes build the active site. In parallel with their unusual structures, the construction (biosynthesis) of the active site proceeds unusually. The first subproject aims to make the first Fe-containing intermediate, Compound B . The next two projects tackle how B is converted to an inorganic Fe-S-CN-CO monomer. The fourth project examines the coupling of this monomer to give an inorganic dimer. The final and fifth project examines the retrofitting of this Fe2 entity with an organic cofactor. In this program collateral projects address allied themes of still broader interest. One involves expanding our knowledge of iron complexes of amino acids. Another contributes to the biosynthesis of [NiFe]-hydrogenases. One spin-off project critically examines the premises of the Iron-Sulfur Theory of the origin of life by examination of the first Fe-S-CN-CO complexes.


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 = $315,340 )
2025	2025	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	24	8/19/2025	NON-COMPETING CONTINUATION	$315,340
														Subtotal = $315,340

Issue Date FY: 2024 ( Subtotal = $315,624 )
2024	2024	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	002	23	8/15/2024	NON-COMPETING CONTINUATION	$315,624
2024	2022	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	21	4/4/2024	COMPETING CONTINUATION	$2
2024	2021	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	20	4/4/2024	NON-COMPETING CONTINUATION	-$2
														Subtotal = $315,624

Issue Date FY: 2023 ( Subtotal = $315,901 )
2023	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	22	8/25/2023	NON-COMPETING CONTINUATION	$315,901
														Subtotal = $315,901

Issue Date FY: 2022 ( Subtotal = $316,170 )
2022	2022	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	21	8/30/2022	COMPETING CONTINUATION	$316,170
2022	2021	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	20	8/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $316,170

Issue Date FY: 2021 ( Subtotal = $308,421 )
2021	2021	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	20	5/11/2021	NON-COMPETING CONTINUATION	$0
2021	2021	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	20	4/19/2021	NON-COMPETING CONTINUATION	$308,421
														Subtotal = $308,421

Issue Date FY: 2020 ( Subtotal = $400,484 )
2020	2020	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	19	6/10/2020	SUPPLEMENT FOR EXPANSION	$91,808
2020	2020	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	19	4/6/2020	NON-COMPETING CONTINUATION	$308,676
														Subtotal = $400,484

Issue Date FY: 2019 ( Subtotal = $308,925 )
2019	2019	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	004	18	4/10/2019	NON-COMPETING CONTINUATION	$308,925
2019	2018	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	003	17	2/10/2019	COMPETING CONTINUATION	$12,490
2019	2018	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	17	10/24/2018	COMPETING CONTINUATION	$0
2019	2018	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	17	10/24/2018	SUPPLEMENT FOR EXPANSION	$0
2019	2017	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	002	16	2/10/2019	NON-COMPETING CONTINUATION	-$12,490
														Subtotal = $308,925

Issue Date FY: 2018 ( Subtotal = $408,165 )
2018	2018	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	17	8/29/2018	SUPPLEMENT FOR EXPANSION	$99,000
2018	2018	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	17	4/12/2018	COMPETING CONTINUATION	$309,165
														Subtotal = $408,165

Issue Date FY: 2017 ( Subtotal = $290,132 )
2017	2017	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	16	4/11/2017	NON-COMPETING CONTINUATION	$261,118
2017	2017	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	16	6/7/2017	NON-COMPETING CONTINUATION	$29,014
														Subtotal = $290,132

Issue Date FY: 2016 ( Subtotal = $290,690 )
2016	2016	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	15	4/29/2016	NON-COMPETING CONTINUATION	$290,690
														Subtotal = $290,690

Issue Date FY: 2015 ( Subtotal = $291,231 )
2015	2015	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	14	4/15/2015	NON-COMPETING CONTINUATION	$291,231
														Subtotal = $291,231

Issue Date FY: 2014 ( Subtotal = $291,756 )
2014	2014	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	001	13	7/18/2014	COMPETING CONTINUATION	$291,756
2014	2013	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	12	7/15/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $291,756

Issue Date FY: 2013 ( Subtotal = $312,733 )
2013	2013	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	001	12	6/20/2013	NON-COMPETING CONTINUATION	$21,065
2013	2013	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	12	12/20/2012	NON-COMPETING CONTINUATION	$291,668
														Subtotal = $312,733

Issue Date FY: 2012 ( Subtotal = $290,716 )
2012	2012	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	002	11	9/3/2012	SUPPLEMENT FOR EXPANSION	$23,830
2012	2012	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	001	11	3/7/2012	NON-COMPETING CONTINUATION	$26,689
2012	2012	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	11	12/16/2011	NON-COMPETING CONTINUATION	$240,197
														Subtotal = $290,716

Issue Date FY: 2011 ( Subtotal = $266,886 )
2011	2011	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	10	12/23/2010	NON-COMPETING CONTINUATION	$242,624
2011	2011	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	001	10	6/6/2011	NON-COMPETING CONTINUATION	$24,262
														Subtotal = $266,886

Issue Date FY: 2010 ( Subtotal = $260,937 )
2010	2010	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	9	11/23/2009	COMPETING CONTINUATION	$260,937
														Subtotal = $260,937

Issue Date FY: 2009 ( Subtotal = $264,691 ) (Continued on the next page)
2009	2009	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	8	12/15/2008	NON-COMPETING CONTINUATION	$212,871
Grand Total All Awards = $6,656,381

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Biosynthesis and Reactivity of the Active Site of the FeFe Hydrogenases

Award Number: R01GM061153

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: 07/01/2000

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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