# Production Scale-Up and Target Identification of the Antioxidant Ergothioneine

> **NIH NIH R41** · ERGO HEALTH, LLC · 2020 · $7,742

## Abstract

ABSTRACT
Ergothioneine is one of the most abundant thiols in many parts of the human body and several diseases have
been linked to ergothioneine insufficiency, including rheumatoid arthritis, Crohn's disease, neurodegenerative
diseases, cardiovascular disorders and diabetes. Animals do not synthesize ergothioneine and, instead, obtain
it from their diet through an ergothioneine-specific transporter (OCTN1) with accumulation up to mM
concentrations in several organs and tissues. Due to their differences in reduction potential (E0' = - 0.06 V for
ergothioneine and E0' = - 0.24 V for glutathione), a combination of ergothioneine and glutathione provide
cellular protection over a wide range of conditions such as against reactive oxygen species (ROS) and reactive
nitrogen species (RNS). Despite ergothioneine's demonstrated role in maintaining human health, the current
method used to produce it has proved to be a bottleneck in its widespread use. Specifically, the chemical
synthesis method suffers from racemization of a stereo-center with the byproduct isomer being toxic. As a
result, production at a large scale is both challenging and costly. In our preliminary studies, we developed an
alternative, fermentation-based biosynthetic production method capable of producing 10 grams/liter on a 1 L
batch-scale. In addition, we have identified the signaling pathway(s) related to ergothioneine function. These
breakthroughs in supply and mechanistic understanding provide the scientific and manufacturing support
necessary to realize ergothioneine's full commercial potential, which includes: further growth of its share in the
cosmetic market, expansion into new markets (e.g., as a component in nutraceuticals), or for drug discovery
and development. In this proposal we will address two key go/no-go questions that will guide the further
development of this product. Specifically, we will scale-up the synthesis to pilot scale production using our
patented ergothioneine production technology and also pinpoint ergothioneine's biological targets. To this end,
the aims are:
 Aim 1: Achieve pilot-scale (100's g – 1 kg) production of ergothioneine with purity >99%.
 Aim 2: Verify the ergothioneine-related signaling pathways.
Outcomes. Upon successful completion of these studies, we will apply for a Phase II grant with aims of large-
scale production under good manufacturing practices to support additional market penetration and expansion.
At the same time, we will re-examine ergothioneine's impact on ageing and age-related disease in vivo. We will
also reach out to other scientists in the anti-ageing field to seek collaboration, including collaboration with an
existing NIH anti-ageing program (https://www.nia.nih.gov/research/dab/interventions-testing-program-itp).

## Key facts

- **NIH application ID:** 10056054
- **Project number:** 3R41AT010878-01S1
- **Recipient organization:** ERGO HEALTH, LLC
- **Principal Investigator:** Pinghua Liu
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $7,742
- **Award type:** 3
- **Project period:** 2019-09-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056054

## Citation

> US National Institutes of Health, RePORTER application 10056054, Production Scale-Up and Target Identification of the Antioxidant Ergothioneine (3R41AT010878-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10056054. Licensed CC0.

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