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A Biosynthetic Strategy to Manufacture Less Toxic Amphotericins

Award Number: F32GM142211
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2022

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A Biosynthetic Strategy to Manufacture Less Toxic Amphotericins - PROJECT ABSTRACT Amphotericin B is a powerful antifungal treatment however, widespread use is prevented by dose limiting toxicity. Nontoxic analogs have been discovered but their structural complexity precludes a practical chemical synthesis on industrial scale. Microbes are extraordinarily adept at producing amphotericin, as metric tons are fermented annually. Enzymes found within amphotericin’s natural biosynthetic pathway can serve as exceptionally specific and renewable biocatalysts that can overcome many common limitations encountered during its chemical synthesis. Reimagining aspects of amphotericin’s biosynthesis could therefore produce a robust and sustainable path to these nontoxic variants. This proposal aims to develop a deep understanding of several catalytic processes involved in amphotericin’s natural biosynthesis. Harnessing this knowledge, key enzymes and biosynthetic pathways will be evolved and engineered to construct a biosynthetic strategy to manufacture less toxic amphotericins. Cell-free protein synthesis provides a means to prototype these enzymes and pathways in a quantitative and high-throughput manner. Ultimately this work is expected to be an efficient platform to create new, best-in-class antifungal candidates, provide probes to interrogate structure-activity relationships dictating AmB’s potency and toxicity, and drive the continued development of enzymes as renewable, ecologically-safe and flexible biocatalysts for pharmaceutical sciences. The proposal provides ample opportunities for me to build on the knowledge from my undergraduate and graduate studies so I may continue to learn, innovate, and develop skills to be a well-rounded scientific leader. Based on the unique scientific expertise and mentoring track record of my Sponsor and Cosponsor, they are the ideal pair to provide constructive guidance in science and career development, and maximize my potential to drive this project towards success.


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: 2023 ( Subtotal = -$46,386 )
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	2	11/9/2022	NON-COMPETING CONTINUATION	-$43,063
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	2	5/15/2023	NON-COMPETING CONTINUATION	-$3,323
														Subtotal = -$46,386

Issue Date FY: 2022 ( Subtotal = $67,582 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	2	5/19/2022	NON-COMPETING CONTINUATION	$1,192
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	2	3/14/2022	NON-COMPETING CONTINUATION	$66,390
														Subtotal = $67,582

Issue Date FY: 2021 ( Subtotal = $65,994 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	1	3/29/2021	NEW	$0
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	1	3/29/2021	NEW	$65,994
														Subtotal = $65,994

Grand Total All Awards = $87,190

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A Biosynthetic Strategy to Manufacture Less Toxic Amphotericins

Award Number: F32GM142211

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2022

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