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Multi-Omics And Synbio Enabled Discovery Of Antifungal Fernene Triterpenes

Award Number: R43AI174407
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Multi-Omics And Synbio Enabled Discovery Of Antifungal Fernene Triterpenes - Project Summary. A new functional metabologenomics approach is proposed for the development of a second generation of fernene-based antifungal terpenes. Our team led by Mead (Varigen), Keller (University of Wisconsin) and Kelleher (Northwestern University) explore the diversity of this unique family of triterpenes using a fusion of technologies that unites genomics with metabolomic understanding of fungal terpene synthesis. We begin by applying a genome mining-driven approach to find new natural analogs of enfumafungin. The resulting data are then integrated with metabolomic analysis and antifungal bioactivity assay data to establish the putative enfumafungin-like metabolites encoded by diverse strains and ultimately chart the structure-activity relationship space within this potent class of antifungals. In parallel, our team is constructing a modular platform capable of generating hundreds of different analogs in functional amounts. Here, we will heterologously express the enfumafungin-like pathways from fungal strains in an engineered Aspergillus nidulans host. The sequence- specific cloning and heterologous expression of lead molecules discovered in this program will establish methods to conduct targeted swapping of cyclase genes across multiple species to generate new antifungal fernene-like scaffolds. The long-term goal, requiring additional resources, is to advance a second generation of triterpene antifungal analogs into the research and clinical market place. Overall, this program provides an important next step towards establishing functional metabologenomics as a viable tool to go from genome to functional therapeutic. As a testbed, we turn to a natural product family with a recent history of clinical utility for the development of new analogs and technologies to access them.


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 = $0 )
2025	2023	VARIGEN BIOSCIENCES CORP	3220 DEMING WAY STE 160	MIDDLETON	WI	53562	DANE	USA	Allergy and Infectious Diseases Research	000	1	6/3/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $300,000 )
2023	2023	VARIGEN BIOSCIENCES CORPORATION	3220 DEMING WAY STE 160	MIDDLETON	WI	53562	DANE	USA	Allergy and Infectious Diseases Research	000	1	3/14/2023	NEW	$300,000
														Subtotal = $300,000

Grand Total All Awards = $300,000

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Multi-Omics And Synbio Enabled Discovery Of Antifungal Fernene Triterpenes

Award Number: R43AI174407

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/15/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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