Monday, June 30, 2025 6/30/2025

Identification, characterization, and application of bacterial site-specific vanadium-dependent haloperoxidase enzymes

Award Number: R35GM147235
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: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Identification, characterization, and application of bacterial site-specific vanadium-dependent haloperoxidase enzymes - Project Summary The incorporation of halogen atoms (F-, Cl-, Br-, I-) in small organic molecules plays a significant role in modulating their physical properties and biological activities while providing a synthetic handle for additional chemical modification. The regioselective and enantioselective installation of halogens in a strictly chemosynthetic manner is technically challenging and frequently utilizes toxic reagents and generates undesirable byproducts. In contrast, Nature has developed efficient enzymatic strategies to incorporate aqueous halide ions into organic scaffolds with negligible waste production. This proposal focuses on the exploration of a unique family of halogenating enzymes, specifically the bacterial site-specific vanadium dependent haloperoxidases (VHPOs), that use a coordinated vanadate ion (VO43-) and co-substrate hydrogen peroxide to oxidize aqueous halide ions and install them in a regio- and stereospecific manner on organic substrates. Despite their involvement in constructing multiple bioactive natural product scaffolds and catalyzing chemically diverse and useful reactions without additional cofactors or coenzymes, only a small fraction of the hundreds of site- specific VHPO homologs have been rigorously characterized. The exploration of this poorly defined chemical and biochemical space is what intellectually drives this proposal. Using interdisciplinary chemical, biochemical, and genomic techniques, we aim to better understand bacterial site-specific VHPO enzymology through three independent, yet interrelated objectives. The first involves the genomic identification and categorization of novel VHPO homologs available within publicly available repositories. Improved representation of microbial site- specific halogenases will permit us to correlate genomic sequences to biochemical reactivities with the ultimate intention of predicting chemistries directly from bioinformatic signatures. The second objective involves understanding the roles of uncharacterized VHPOs within bacterial secondary metabolism and chemical ecology. The majority of known bacterial site-specific homologs catalyze chemically unique reactions in natural product biosynthetic pathways; these biochemistries are critical for establishing the bioactivities of their cognate products. We propose that novel VHPO reactivities and diverse substrate scaffolds remain to be discovered, and that the use of homologous genes as biosynthetic ‘hooks’ will facilitate the genome-based identification of new secondary metabolites. Finally, we aim to define the structural determinants of halide and organic substrate specificity for synthetic applications, either within their native substrates or expanded to novel scaffolds. These objectives will simultaneously improve our understanding of VHPO halogenation enzymology at the substrate and macromolecular level and will facilitate biocatalytic efforts to apply these site-specific microbial halogenases towards chemically useful transformations.


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 = $372,762 )
2025	2025	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	4	5/26/2025	NON-COMPETING CONTINUATION	$372,762
														Subtotal = $372,762

Issue Date FY: 2024 ( Subtotal = $372,762 )
2024	2024	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	3	5/2/2024	NON-COMPETING CONTINUATION	$372,762
														Subtotal = $372,762

Issue Date FY: 2023 ( Subtotal = $372,762 )
2023	2023	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	2	5/16/2023	NON-COMPETING CONTINUATION	$372,762
														Subtotal = $372,762

Issue Date FY: 2022 ( Subtotal = $372,762 )
2022	2022	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	1	7/11/2022	NEW	$372,762
														Subtotal = $372,762

Grand Total All Awards = $1,491,048

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identification, characterization, and application of bacterial site-specific vanadium-dependent haloperoxidase enzymes

Award Number: R35GM147235

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: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer