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The Structural Basis for Modular Nonribosomal Peptide Synthesis

Award Number: R01GM116957
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: 01/01/2016
PERIOD OF PERFORMANCE END DATE: 12/31/2019

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The Structural Basis for Modular Nonribosomal Peptide Synthesis - ¿ DESCRIPTION (provided by applicant): Natural products are a rich source of pharmaceutically active compounds. One class of natural products are produced by the non-ribosomal peptide synthetases (NRPSs) through a fascinating modular, multidomain architecture. During synthesis, the peptide intermediates are bound to an integrated carrier protein that is delivered in a coordinated manner to neighboring catalytic domains. A complete understanding of the NRPS structural enzymology, including the active sites and the domain interfaces, would allow the identification of novel products both through analysis and prediction of uncharacterized biosynthetic clusters and the engineering of novel chemical moieties into previously identified NRPSs. To continue our structural interrogation of NRPSs, we will determine structures of NRPS multidomain enzymes, including full-length modules, with informative ligands. Our studies will address multiple NRPS systems that perform standard and unusual peptide syntheses. We will additionally examine the structural basis of a family of small auxiliary proteins that enhance NRPS adenylation domains. And finally, we will examine cytotoxin production from a novel NRPS system from a human commensal bacteria. These studies will use biochemical, biophysical, structural, and chemical techniques to continue our work to provide a complete structural description of the active sites and the domain choreography of the modular NRPS enzymes.


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: 2022 ( Subtotal = $0 )
2022	2018	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	3	9/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = -$6 )
2021	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	000	5	5/6/2021	NON-COMPETING CONTINUATION	-$6
														Subtotal = -$6

Issue Date FY: 2019 ( Subtotal = $305,935 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	002	5	12/28/2018	NON-COMPETING CONTINUATION	$326,805
2019	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	001	4	11/30/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$312,601
2019	2018	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	003	3	3/28/2019	NON-COMPETING CONTINUATION	-$1,257
2019	2018	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	3	11/30/2018	NON-COMPETING CONTINUATION	-$333,471
2019	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	004	4	3/28/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,257
														Subtotal = $305,935

Issue Date FY: 2018 ( Subtotal = $389,816 )
2018	2018	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	3	12/7/2017	NON-COMPETING CONTINUATION	$350,834
2018	2018	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	001	3	5/22/2018	NON-COMPETING CONTINUATION	$38,982
														Subtotal = $389,816

Issue Date FY: 2017 ( Subtotal = $388,239 )
2017	2017	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	001	2	6/13/2017	NON-COMPETING CONTINUATION	$38,824
2017	2017	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	2	12/7/2016	NON-COMPETING CONTINUATION	$349,415
														Subtotal = $388,239

Issue Date FY: 2016 ( Subtotal = $405,587 )
2016	2016	HAUPTMAN-WOODWARD MEDICAL RESEARCH INSTITUTE, INC	700 Ellicott St	Buffalo	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	1	12/1/2015	NEW	$405,587
														Subtotal = $405,587

Grand Total All Awards = $1,489,571

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The Structural Basis for Modular Nonribosomal Peptide Synthesis

Award Number: R01GM116957

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: 01/01/2016

PERIOD OF PERFORMANCE END DATE: 12/31/2019

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