You are here

Production Scale-Up and Target Identification of the Antioxidant Ergothioneine

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AT010878-01
Agency Tracking Number: R41AT010878
Amount: $225,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NCCIH
Solicitation Number: PA18-575
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-01
Award End Date (Contract End Date): 2020-08-31
Small Business Information
Auburndale, MA 02466
United States
DUNS: 079624637
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 353-2481
Business Contact
Phone: (617) 353-2481
Research Institution
BOSTON, MA 02215-1390
United States

 Nonprofit College or University

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, Crohnandapos;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 (E0andapos; = - 0.06 V for
ergothioneine and E0andapos; = - 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 ergothioneineandapos;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 ergothioneineandapos;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 ergothioneineandapos;s biological targets. To this end,
the aims are:Aim 1: Achieve pilot-scale (100andapos;s g – 1 kg) production of ergothioneine with purity andgt;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 ergothioneineandapos;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 (
Ergothioneine is one of the most abundant antioxidants in many parts of the human body and researchers
have suggested that several diseases may be related to ergothioneine insufficiency, including rheumatoid
arthritis, Crohnandapos;s disease, some neurodegenerative diseases, cardiovascular disorders and diabetes. However,
the therapeutic potential of ergothioneine is as yet untapped due to an inability to produce ergothioneine at
affordable prices on a large scale. This proposal seeks to solve this issue of production and, in so doing,
enable both further research into the biological targets of ergothioneine (this grant) and human health (other
researchers) as well as incorporation into cosmetics, nutraceuticals, pharmaceuticals or other supplements to
improve human health.

* Information listed above is at the time of submission. *

US Flag An Official Website of the United States Government