# Engineering probiotic yeast for efficient sulforaphane delivery

> **NIH NIH R43** · BERKELEY FERMENTATION SCIENCE INC. · 2020 · $325,000

## Abstract

Project Summary / Abstract for WS00393217
Principal Investigator: Charles Denby, PhD (BFS)
Engineering probiotic yeast for efficient sulforaphane delivery
Consumption of cruciferous vegetables such as broccoli, brussels sprouts, and cauliflower has been shown
to reduce the risk of developing multiple forms of cancer. Recent research has suggested that these health
benefits result in part from the biochemical activity of isothiocyanates, a class of natural products found in
these vegetables. Sulforaphane (SFN), one such isothiocyanate produced in abundance by crucifers like
broccoli and kale, has shown especially impressive potential as a chemo-preventative and cancer therapeutic
in in vitro and animal model studies. It has been challenging to rigorously assess the health benefits of SFN in
humans, however. These challenges result from SFN’s inherent instability, as well as the varying effects that
different food preparation methods and personal microbiome compositions have on SFN bioavailability. In this
STTR, we propose to engineer a probiotic yeast that will biosynthesize SFN from within the human
gastrointestinal tract. This probiotic yeast will provide a consistent and direct source of SFN that readily
diffuses into the bloodstream, and is not dependent on specific microbiome compositions, food preparation
methods, or drug regimens. Given the impressive body of research detailing the potential for SFN to treat
prostate cancer in cell culture and animal models, we will develop this probiotic for potential use as a prostate
cancer therapeutic. The probiotic microbe we will use as a host for our engineering efforts is the safe, and
genetically tractable probiotic yeast, S. boulardii. The engineered S. boulardii strain will provide a means to
directly assess the health benefits of SFN in prostate cancer therapy, while also providing a mechanism to
efficiently deliver SFN for cancer therapeutic and preventative purposes. Phase I experiments will develop a
S. boulardii strain that secretes a highly active myrosinase enzyme that is able to perform the terminal step in
SFN biosynthesis. To achieve this goal, we will screen libraries of myrosinases, secretion signals, and yeast
promoters to identify the genetic components that most effectively produce SFN under gastrointestinal
conditions. To establish a proof-of-principle and motivate further research, Phase I will seek to engineer
S. boulardii for production of 200 µmoles SFN per day, as small clinical trials that administered this quantity
have shown encouraging results. In Phase II research, we will further engineer S. boulardii such that it contains
the entire SFN biosynthesis pathway and produces SFN from fermentable sugars. Resultant strains will be
tested in prostate cancer mouse models for safety and cancer-preventive properties. This project is directly in
line with the NCI mission, as it will advance our understanding of a promising cancer therapeutic molecule,
while also providing a direct...

## Key facts

- **NIH application ID:** 10080522
- **Project number:** 1R43AT011168-01
- **Recipient organization:** BERKELEY FERMENTATION SCIENCE INC.
- **Principal Investigator:** Charles Denby
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $325,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080522

## Citation

> US National Institutes of Health, RePORTER application 10080522, Engineering probiotic yeast for efficient sulforaphane delivery (1R43AT011168-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10080522. Licensed CC0.

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