Wednesday, January 28, 2026 1/28/2026

Biosynthesis of Cyclopamine and New-to-Nature Triterpenoids in Yeast

Award Number: F32GM153046
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Biosynthesis of Cyclopamine and New-to-Nature Triterpenoids in Yeast - Project Summary/Abstract The scalable and sustainable biosynthesis of terpenoid drugs like cyclopamine and diverse libraries of terpenoid drug candidates will transform the treatment of disease. There are >30,000 unique plant terpenoids and a valuable subset of these natural products have been approved by the FDA approved or are currently in clinical trials for cancer treatment, malaria treatment, symptom relief, and immune system activation. Terpenoids can be biosynthesized in plants through expensive cultivation (i.e., time-, labor-, and land-intensive), but these approaches can exhibit low and hypervariable yields. Plant terpenoids can also be produced by chemical total synthesis and semi-synthesis. However, terpenoids can contain many chiral centers (e.g., 10 in cyclopamine), resulting in complex syntheses with low overall yields. In contrast, the production of terpenoids in engineered microorganisms is scalable, renewable, and inexpensive, often producing complex terpenoids from simple sugars and salts. For example, an artemisinic acid-producing yeast has resulted in 51 million treatments of artemisinin, contributing to the low current cost of artemisinin anti-malarial combination therapies. This proposal aims to establish methods to accelerate the future microbial biosynthesis of medicinal terpenoids. The full 30-step biosynthetic pathway for cyclopamine will be constructed step-by-step in the brewer’s yeast (Saccharomyces cerevisiae) to produce cyclopamine from simple sugars and salts and solve the challenge of sourcing this drug for the treatment of cancer. In addition, S. cerevisiae will be engineered to produce sets of new-to-nature triterpenoids through the combinatorial screening of enzymes with well-characterized activity. The studies will accelerate the microbial biosynthesis of medicinal terpenoids and diverse libraries of terpenoid drug candidates.


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 = $79,276 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	3	1/19/2026	NON-COMPETING CONTINUATION	$78,040
2026	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	2	1/21/2026	NON-COMPETING CONTINUATION	$1,236
														Subtotal = $79,276

Issue Date FY: 2025 ( Subtotal = $74,284 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	2	2/28/2025	NON-COMPETING CONTINUATION	$74,284
														Subtotal = $74,284

Issue Date FY: 2024 ( Subtotal = $73,828 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	1	12/20/2023	NEW	$0
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	1	12/20/2023	NEW	$69,080
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	002	1	5/14/2024	NEW	$4,748
														Subtotal = $73,828

Grand Total All Awards = $227,388

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Biosynthesis of Cyclopamine and New-to-Nature Triterpenoids in Yeast

Award Number: F32GM153046

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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