Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Discovery and Characterization of Manganese-dependent Monooxygenases

Award Number: R01GM153888
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: 03/15/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2029

Group Awards By:

View Award Description

Discovery and Characterization of Manganese-dependent Monooxygenases - Project Summary The oxidation of carbon-hydrogen (C-H) bonds is a central biochemical process required by all aerobic organisms. The microbial conversion of these bonds endows potent bioactivity on natural products and enable pathogens to thrive on otherwise inert host-derived biomolecules. These reactions are currently known to be accomplished by a short list of cofactors that include heme, nonheme iron, and copper. While manganese cofactors perform difficult oxidation reactions, including water oxidation within Photosystem II, they are generally not known to be used for C-H bond activation. We recently discovered that the 2-aminoisobutyric acid hydroxylase from Rhodococcus wratislaviensis, AibH1H2, requires manganese to functionalize a strong, aliphatic C-H bond (BDE = 100 kcal/mol). Structural and spectroscopic studies of this enzyme revealed a redox- active, heterobimetallic manganese-iron active site at the locus of O2 activation and substrate coordination. This result expands the known reactivity of biological manganese-iron cofactors, which was previously restricted to single electron transfer or stoichiometric protein oxidation. Since the AibH1H2 cofactor is supported by a protein fold distinct from typical, well-studied bimetallic oxygenases, our proposed research centers on the characterization of ill-defined members of this protein family. Our preliminary results indicate that many of these proteins harbor two active-site metal ions, behave as monooxygenases and, in some cases, display enhanced enzymatic activity when manganese ions are preferentially incorporated within the active site. The core scientific hypothesis for this study is that the unique sequence and structural features of this emergent class of monooxygenases endows embedded manganese ions with otherwise unknown biological reactivity. To investigate this hypothesis, the specific aims of this study are to (1) understand the signature amino acid motifs that differentiate these monooxygenases from their ancestral, structurally-related amidohydrolases, (2) characterize the geometric and electronic structures of mixed iron/manganese-containing enzymatic intermediates, and (3) evaluate the thermodynamic and kinetic competence of cambialistic Mn/Fe monooxygenases. The resulting enzymatic information, methods, and structures will be of specific interest to those in the fields of metallo-enzymology, structural biology, and synthetic bioinorganic chemistry, and of broad interest to microbiologists in general.


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 = $338,876 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	3	2/6/2026	NON-COMPETING CONTINUATION	$304,989
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	001	3	3/11/2026	NON-COMPETING CONTINUATION	$33,887
														Subtotal = $338,876

Issue Date FY: 2025 ( Subtotal = $338,876 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	2	2/20/2025	NON-COMPETING CONTINUATION	$304,989
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	2	8/13/2025	NON-COMPETING CONTINUATION	$33,887
														Subtotal = $338,876

Issue Date FY: 2024 ( Subtotal = $547,711 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	1	3/7/2024	NEW	$338,876
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	1	9/10/2024	SUPPLEMENT FOR EXPANSION	$208,835
														Subtotal = $547,711

Grand Total All Awards = $1,225,463

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Discovery and Characterization of Manganese-dependent Monooxygenases

Award Number: R01GM153888

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: 03/15/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer