# Engineering probiotic yeast for efficient sulforaphane delivery

> **NIH NIH R43** · BERKELEY FERMENTATION SCIENCE INC. · 2021 · $52,000

## Abstract

Project Summary/Abstract
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. Sulflurophane (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
SBIR, 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 we develop 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 an 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, secretin
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 200umoles 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 NIH mission, as it will advance our understanding of a promising cancer therapeutic
molecule, while also providing a direct means of delivering this potential therapeutic for cancer therapy and
prevention.

## Key facts

- **NIH application ID:** 10305158
- **Project number:** 3R43AT011168-01S1
- **Recipient organization:** BERKELEY FERMENTATION SCIENCE INC.
- **Principal Investigator:** Charles Denby
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $52,000
- **Award type:** 3
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10305158

## Citation

> US National Institutes of Health, RePORTER application 10305158, Engineering probiotic yeast for efficient sulforaphane delivery (3R43AT011168-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10305158. Licensed CC0.

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