Wednesday, December 3, 2025 12/3/2025

Characterization of YcaO-Dependent Natural Product Biosynthetic Pathways

Award Number: R01GM097142
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: 02/01/2012
PERIOD OF PERFORMANCE END DATE: 07/31/2024

Group Awards By:

View Award Description

Characterization of YcaO-Dependent Natural Product Biosynthetic Pathways - Our group is broadly interested in the chemical biology of natural products with a strong focus on genomics- based discovery, biosynthetic mechanistic enzymology, and determination of structure-activity relationships and mode of action. Beyond their historical impact on medicine, natural products have inspired generations of syn- thetic chemists and provided the necessary chemical probes to illuminate fundamental aspects of biology. One natural product family that has received increased attention over the past several years are the ribosomally synthesized and post-translationally modified peptides (RiPPs). While there are over 30 distinct structural clas- ses of RiPP natural products reported, they are united by a common biosynthetic logic: a precursor peptide, typically composed of an N-terminal leader and a C-terminal core, is ribosomally produced. The leader region contains motifs that are recognized by the modification enzymes and the core region is where the modifications take place. Upon maturation, the leader region is often removed prior to cellular export. The current project focuses on natural product biosynthetic pathways that encode a member of the YcaO superfamily. During the original funding period, we showed that YcaO enzymes were responsible for the ATP- dependent activation of the peptide backbone to yield azoline heterocycles from Cys, Ser, and Thr residues of the core peptide. During the current funding period, we discovered that two additional reaction types are cata- lyzed by YcaO enzymes: thioamidation and macrolactamidation of the peptide backbone. No fewer than five classes of RiPPs are now known to utilize a member of the YcaO superfamily, namely the linear azol(in)e- containing peptides, thiopeptides, cyanobactins, bottromycins, and thioviridamides. Despite a wealth of knowledge, we can only predict the modification type of approximately one-third of the YcaO superfamily. Our bioinformatics analysis suggests that several new reaction types remain to be discovered. For this renewal project, we tackle several outstanding questions with respect to YcaO-dependent natural product biosynthesis. Aim I focuses on the structurally and enzymatically intriguing thiopeptide RiPP class. Aim IA will overcome biosynthetic bottlenecks with respect to substrate tolerance in order to establish the elusive structure-activity relationships and generate advanced biosynthetic intermediates that will enable the study of late-stage transformations found within the class. Aim IB will determine the enzymatic mechanism and substrate scope of the class-defining [4+2]-cycloaddition and establish why some are pyridine-forming while others are dehydropiperidine-forming. Aim II focuses on peptide backbone thioamidation, in particular, deciphering the func- tion of the TfuA partner protein and a novel desulfurase/lysase involved in mobilizing sulfur from Cys. Lastly, Aim III characterizes divergent YcaO family members that appear in unique genomic contexts to discover new reac- tions catalyzed by the superfamily. Our preliminary data, rich environment, and strong investigative team place us in an ideal position to address these aims.


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: 2026 ( Subtotal = $0 )
2026	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	12	10/29/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = -$360,561 )
2025	2024	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	003	13	4/23/2025	COMPETING CONTINUATION	-$381,143
2025	2024	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	11	3/26/2025	SUPPLEMENT FOR EXPANSION	-$381,143
2025	2024	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	002	13	3/26/2025	COMPETING CONTINUATION	$97,974
2025	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	004	14	4/23/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$401,725
2025	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	006	14	8/20/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Biomedical Research and Research Training	005	14	7/4/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	11	3/26/2025	SUPPLEMENT FOR EXPANSION	-$3,399
2025	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	12	3/26/2025	NON-COMPETING CONTINUATION	-$94,575
														Subtotal = -$360,561

Issue Date FY: 2024 ( Subtotal = $381,144 )
2024	2024	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	13	9/9/2024	COMPETING CONTINUATION	$381,144
														Subtotal = $381,144

Issue Date FY: 2023 ( Subtotal = $337,890 )
2023	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	12	7/19/2023	NON-COMPETING CONTINUATION	$326,169
2023	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	11	5/16/2023	SUPPLEMENT FOR EXPANSION	$11,721
														Subtotal = $337,890

Issue Date FY: 2022 ( Subtotal = $326,169 )
2022	2022	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	11	7/13/2022	NON-COMPETING CONTINUATION	$326,169
														Subtotal = $326,169

Issue Date FY: 2021 ( Subtotal = $412,355 )
2021	2021	UNIVERSITY OF ILLINOIS	352 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	002	9	7/13/2021	SUPPLEMENT FOR EXPANSION	$70,862
2021	2021	UNIVERSITY OF ILLINOIS	352 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	003	10	7/28/2021	NON-COMPETING CONTINUATION	$341,493
2021	2020	UNIVERSITY OF ILLINOIS	352 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	9	7/3/2021	COMPETING CONTINUATION	$27,620
2021	2019	UNIVERSITY OF ILLINOIS	352 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	8	7/3/2021	NON-COMPETING CONTINUATION	-$27,620
														Subtotal = $412,355

Issue Date FY: 2020 ( Subtotal = $337,662 )
2020	2020	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	9	7/20/2020	COMPETING CONTINUATION	$337,662
2020	2019	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	8	7/10/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $337,662

Issue Date FY: 2019 ( Subtotal = $302,746 )
2019	2019	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	8	7/16/2019	NON-COMPETING CONTINUATION	$302,746
														Subtotal = $302,746

Issue Date FY: 2018 ( Subtotal = $303,297 )
2018	2018	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	7	7/11/2018	NON-COMPETING CONTINUATION	$303,297
														Subtotal = $303,297

Issue Date FY: 2017 ( Subtotal = $303,831 )
2017	2017	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	004	6	7/19/2017	NON-COMPETING CONTINUATION	$303,831
2017	2016	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	5	1/21/2017	COMPETING CONTINUATION	$7,908
2017	2016	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	003	5	4/13/2017	COMPETING CONTINUATION	$7,859
2017	2015	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	4	1/21/2017	NON-COMPETING CONTINUATION	-$7,908
2017	2015	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	002	4	4/13/2017	NON-COMPETING CONTINUATION	-$7,859
														Subtotal = $303,831

Issue Date FY: 2016 ( Subtotal = $304,350 )
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	001	5	8/1/2016	COMPETING CONTINUATION	$304,350
2016	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	4	7/27/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $304,350

Issue Date FY: 2015 ( Subtotal = $276,447 )
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	4	1/14/2015	NON-COMPETING CONTINUATION	$276,447
														Subtotal = $276,447

Issue Date FY: 2014 ( Subtotal = $272,797 )
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	000	3	3/26/2014	NON-COMPETING CONTINUATION	$272,797
														Subtotal = $272,797

Issue Date FY: 2013 ( Subtotal = $259,097 )
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	2	6/20/2013	NON-COMPETING CONTINUATION	$17,452
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	2	1/15/2013	NON-COMPETING CONTINUATION	$241,645
														Subtotal = $259,097

Issue Date FY: 2012 ( Subtotal = $257,599 )
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	1	1/31/2012	NEW	$257,599
														Subtotal = $257,599

Grand Total All Awards = $3,714,823

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Characterization of YcaO-Dependent Natural Product Biosynthetic Pathways

Award Number: R01GM097142

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: 02/01/2012

PERIOD OF PERFORMANCE END DATE: 07/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer