Monday, September 15, 2025 9/15/2025

Understanding the specificity and non-native catalytic activity of PLP-dependent enzymes

Award Number: R35GM151205
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: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Understanding the specificity and non-native catalytic activity of PLP-dependent enzymes - Project Summary PLP-dependent enzymes are one of the most versatile biocatalysts and catalyze a diverse range of chemical transformations. They are widespread in nature and play critical roles in metabolism and numerous cellular processes. Studying PLP enzymes is hence important for us to understand biology and develop therapeutics. Because of their exquisite and versatile catalytic activity, PLP-dependent enzymes are also remarkable biocatalysts to build diverse structurally complex and bioactive natural products; and are indispensable biocatalytic tools for asymmetric synthesis of noncanonical amino acids and chiral amine pharmaceuticals. However, despite the vast number of PLP-dependent enzymes characterized to date, our abilities to predict, manipulate, and harness their activities are still largely limited. This research program desires to fill the knowledge gap by integrating discovery, mechanistic investigation, and biocatalytic application to systematically and comprehensively study four types of carbon-carbon (C-C) bond forming and cleaving PLP enzymes, including our recently discovered PLP-dependent Mannich cyclase. These enzymes represent the frontier of PLP enzymology because of their unusual activity, complementary synthetic utility to existing biocatalysts, and unexpected evolutionary relationship with well-characterized PLP enzyme family. All proposed aims are supported by strong preliminary data gathered in our laboratory. Our overarching goal is to understand the chemical and substrate specificity and leverage this understanding to uncover previously unknown functions of PLP-dependent enzymes and explore their non-native catalytic utility. Ultimately, the proposed research will expand our mechanistic understanding on PLP enzymology, shed new light on metabolism, and provide novel biocatalytic tools for amino acid biosynthesis.


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 = $467,086 )
2025	2025	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Biomedical Research and Research Training	000	3	8/18/2025	NON-COMPETING CONTINUATION	$376,226
2025	2025	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Biomedical Research and Research Training	001	3	8/19/2025	SUPPLEMENT FOR EXPANSION	$90,860
														Subtotal = $467,086

Issue Date FY: 2024 ( Subtotal = $560,872 )
2024	2024	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Biomedical Research and Research Training	002	2	8/13/2024	SUPPLEMENT FOR EXPANSION	$75,716
2024	2024	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Biomedical Research and Research Training	001	2	5/21/2024	NON-COMPETING CONTINUATION	$376,804
2024	2024	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Biomedical Research and Research Training	000	1	4/26/2024	SUPPLEMENT FOR EXPANSION	$108,352
														Subtotal = $560,872

Issue Date FY: 2023 ( Subtotal = $377,350 )
2023	2023	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Biomedical Research and Research Training	000	1	7/17/2023	NEW	$377,350
														Subtotal = $377,350

Grand Total All Awards = $1,405,308

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Understanding the specificity and non-native catalytic activity of PLP-dependent enzymes

Award Number: R35GM151205

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: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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