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Engineering Specialized Organelles in Yeast for Compartmentalized Production of Therapeutics

Award Number: R35GM164064
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: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Engineering Specialized Organelles in Yeast for Compartmentalized Production of Therapeutics - Project Summary/Abstract Eukaryotic cells utilize organelles to compartmentalize biochemical processes, ensuring spatial control over complex metabolism. This project aims to re-engineer the peroxisome and vacuole organelles to be synthetic, specialized organelles for engineered metabolic pathways. Accordingly, this project has significance both in directly testing, and likely expanding, the current understanding of the biology of these organelles and in the engineering of platform strains that will enable the unicellular microbe Saccharomyces cerevisiae to mimic the tissue compartmentalization observed in many plants for the synthesis of many natural products used as therapeutics in the clinic. Specifically, the reprogramming of the following key organelle properties will be targeted: organelle biogenesis and morphology, membrane permeability to small molecules, rate and efficiency of soluble protein import, and membrane protein trafficking to gain selective small molecule import/export. These engineering efforts will establish design rules for these organelle functions as well as develop powerful tools for the metabolic engineering of complex, therapeutic molecules with the preferred fermentation host, Saccharomyces cerevisiae. Accordingly, this unicellular microbe can be a chassis capable of compartmentalizing parts of a pathway in the peroxisome, vacuole, and cytoplasm. In the proposed work, increased flux through the benzylisoquinoline alkaloid pathway and control over which products are biosynthesized will be achieved using the specialized organelles engineered in this work.


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 = $387,596 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	1	5/20/2026	NEW	$387,596
														Subtotal = $387,596

Grand Total All Awards = $387,596

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Engineering Specialized Organelles in Yeast for Compartmentalized Production of Therapeutics

Award Number: R35GM164064

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: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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