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Biosynthesis and Mining of Amino Acid-derived Natural Products in Fungi

Award Number: R35GM118056
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: 05/01/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Biosynthesis and Mining of Amino Acid-derived Natural Products in Fungi - ABSTRACT Natural products (NPs) are small molecules that have diverse biological activities and have been used in human health applications. The biosynthesis of natural products is performed by the coordinated activities of enzymes that together form a biosynthetic pathway. Our laboratory is interested in genome-guided natural product and enzyme discovery, driven by looking for answers to three overarching questions: i) what is Nature’s chemical logic in generation of complex structures seen in NPs? ii) how to prioritize the vast genome information to identify new families of NPs that have not been discovered in the last half-century? and iii) can fundamentally new enzymology be discovered and exploited for genome mining and biocatalysis? In this funding period, our lab will focus on two research areas. In area 1, we will investigate pathways that involve dimeric binuclear copper-dependent oxidases (BNCuO), a large and entirely new class of metalloenzymes involved in fungal natural product biosynthesis. We have provided the first biochemical characterization of members of this family, which opens up significant opportunities for both fundamental enzymology and pathway exploration. Experiments aimed at enhanced functional expression, detailed characterization, and genome mining will be performed. Collectively, these efforts will lead to insights into the sequence- function relationships of these enzymes, and provide the community with tools to explore the vast number of pathways involving BNCuO enzymes. In area 2, we will investigate and mine amino acid-derived NPs that are not biosynthesized from well-characterized core enzymes, such as nonribosomal peptide synthetase (NRPS) and ribosomally synthesized and post- translationally modified peptides (RiPPs). These NPs are instead generated from new core- forming enzymes, and represent new frontiers for biosynthetic investigation. We will first focus on known amino acid-derived natural products that are clearly assembled from yet unknown bond-forming logic. This will be followed by leveraging the findings to mine new compounds and biological activity.


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 = $592,508 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	11	2/20/2026	COMPETING CONTINUATION	$592,508
2026	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	10	2/12/2026	TERMINATION	$0
2026	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	10	1/29/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $592,508

Issue Date FY: 2025 ( Subtotal = $586,073 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	10	6/16/2025	NON-COMPETING CONTINUATION	$586,073
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	004	10	7/16/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	9	11/19/2024	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	003	9	7/16/2025	TERMINATION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	9	6/16/2025	TERMINATION	$0
														Subtotal = $586,073

Issue Date FY: 2024 ( Subtotal = $605,865 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	9	3/12/2024	SUPPLEMENT FOR EXPANSION	$19,792
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	9	8/5/2024	NON-COMPETING CONTINUATION	$58,607
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	9	3/11/2024	NON-COMPETING CONTINUATION	$527,466
														Subtotal = $605,865

Issue Date FY: 2023 ( Subtotal = $837,011 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	8	3/9/2023	SUPPLEMENT FOR EXPANSION	$79,165
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	8	6/28/2023	SUPPLEMENT FOR EXPANSION	$171,773
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	3/7/2023	NON-COMPETING CONTINUATION	$586,073
														Subtotal = $837,011

Issue Date FY: 2022 ( Subtotal = $645,447 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	7	7/19/2022	SUPPLEMENT FOR EXPANSION	$59,374
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	7	6/28/2022	NON-COMPETING CONTINUATION	$58,607
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	7	3/10/2022	NON-COMPETING CONTINUATION	$527,466
														Subtotal = $645,447

Issue Date FY: 2021 ( Subtotal = $586,073 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	6	8/13/2021	COMPETING CONTINUATION	$192,998
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	6	3/26/2021	COMPETING CONTINUATION	$586,073
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	5	8/13/2021	NON-COMPETING CONTINUATION	-$192,998
														Subtotal = $586,073

Issue Date FY: 2020 ( Subtotal = $558,403 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	2/18/2020	NON-COMPETING CONTINUATION	$558,403
														Subtotal = $558,403

Issue Date FY: 2019 ( Subtotal = $635,205 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	001	4	8/7/2019	SUPPLEMENT FOR EXPANSION	$76,734
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	3/11/2019	NON-COMPETING CONTINUATION	$558,471
														Subtotal = $635,205

Issue Date FY: 2018 ( Subtotal = $558,538 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	001	3	5/25/2018	NON-COMPETING CONTINUATION	$55,856
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	2/23/2018	NON-COMPETING CONTINUATION	$502,682
														Subtotal = $558,538

Issue Date FY: 2017 ( Subtotal = $477,617 )
2017	2017	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	3/10/2017	NON-COMPETING CONTINUATION	$429,854
2017	2017	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	6/15/2017	NON-COMPETING CONTINUATION	$47,763
														Subtotal = $477,617

Issue Date FY: 2016 ( Subtotal = $37,861 )
2016	2016	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	4/14/2016	NEW	$37,861
														Subtotal = $37,861

Grand Total All Awards = $6,120,601

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Biosynthesis and Mining of Amino Acid-derived Natural Products in Fungi

Award Number: R35GM118056

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: 05/01/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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