Ergothioneine
0 plants or animals that synthesize ergothioneine
A 2014 genomic survey of the tree of life found the ergothioneine biosynthesis gene in nearly every fungal phylum — and in no plant or animal genome anywhere.
Jones et al., Gene, 2014
Fungi only
the only kingdom with the Egt1 biosynthesis gene in all major phyla
Bacteria first
fungi acquired ergothioneine synthesis via horizontal gene transfer from actinobacteria
Mushrooms, primarily
the richest dietary source by a wide margin — porcini and king oyster highest
Jones et al., Gene, 2014
View as image ↗Something unusual happened in the evolutionary history of ergothioneine. The compound is made by fungi and some bacteria. Animals cannot make it. Plants cannot make it. Yet the human body evolved a dedicated molecular transporter, OCTN1, whose sole documented purpose is to absorb ergothioneine and concentrate it in the tissues that need protection most.
You don't build specialized machinery to collect something that doesn't matter. The fact that evolution preserved and strengthened this transporter over millions of years — while never once giving us the ability to make ergothioneine ourselves — is the strongest biological signal we have that this compound plays an irreplaceable role.
Understanding why only fungi synthesize ergothioneine explains both why mushrooms are nutritionally unusual and what happens in populations that rarely eat them. The broader case for why ergothioneine matters is covered in What Is Ergothioneine? The Amino Acid Your Body Hoards. This article is specifically about the synthesis side: where ergothioneine comes from, how it's made, and what the absence of that capacity in all other kingdoms means.
Key Takeaways
- Jones et al. (2014) surveyed the tree of life and found the Egt1 ergothioneine biosynthesis gene in nearly all fungal phyla — but in no plant, no animal, and no archaeal genome
- Fungi acquired the ability to make ergothioneine through horizontal gene transfer from actinobacteria (soil bacteria); the pathway predates the fungal kingdom itself
- One exception within fungi: Saccharomycotina — the yeast group that includes baker's yeast and brewer's yeast — lacks the Egt1 gene, meaning most commercial yeasts do not produce ergothioneine
- Kalaras et al. (2017) established that mushrooms are by far the richest dietary source of ergothioneine, with porcini and king oyster mushrooms at the top of the ranking
- Ergothioneine and glutathione co-occur in mushrooms at concentrations far higher than in any other food tested by the Kalaras team
- Ames (2018) proposed that dietary ergothioneine is a longevity vitamin — not a nutrient that causes deficiency disease when absent, but one whose chronic shortage may accelerate aging-related decline
Three Reasons Only Fungi Synthesize Ergothioneine
The simplest answer, before the mechanisms: the enzyme required to build ergothioneine from its raw materials exists in fungal DNA and in some bacterial DNA. It does not exist in any plant or animal genome.
The slightly deeper answer, for anyone who wants to understand it:
1. The biosynthesis pathway requires two enzymes that no plant or animal has ever evolved. The first enzyme, Egt1, converts a methylated form of histidine into an intermediate compound by attaching a sulfur atom derived from cysteine. The second enzyme, Egt2, completes the structure. Both enzymes are absent from all plant and animal genomes. Without them, there is no metabolic route to ergothioneine, regardless of what raw materials are available.[1]
2. Fungi acquired this pathway from bacteria — they didn't invent it independently. Jones and colleagues' 2014 genomic analysis traced the evolutionary history of Egt1 and found that fungi originally acquired it through horizontal gene transfer from actinobacteria. This means ergothioneine synthesis has bacterial origins that predate the fungal kingdom, and fungi are the branch of the tree of life that inherited it and kept it.[1]
3. Humans (and all animals) have no biosynthesis pathway — dietary acquisition via fungi is the only option. For animals, the only route to ergothioneine is eating foods that contain it. Since mushrooms are the most concentrated dietary source by a substantial margin, populations that eat few or no mushrooms are working from a narrow supply base.
The Genome Evidence: How Scientists Mapped This Across the Tree of Life
The most systematic examination of ergothioneine biosynthesis distribution was published by Jones and colleagues in 2014 in the journal Gene.
Jones's team surveyed publicly available genome databases across the major branches of the tree of life — bacteria, archaea, fungi, plants, and animals — looking specifically for the genes encoding the Egt1 and Egt2 enzymes.[1]
The distribution they found was striking. Egt1 appeared in essentially all major fungal phyla: Basidiomycota (the group that includes mushrooms), Ascomycota (the largest fungal phylum), and the other deep fungal lineages. The one notable exception within fungi was Saccharomycotina, the subgroup that includes Saccharomyces cerevisiae — baker's yeast, brewer's yeast, and most commercial yeasts. This entire subgroup had lost the Egt1 gene at some point in its evolutionary history.[1]
Outside of fungi, Jones found Egt1 in actinobacteria (the bacterial group that includes Mycobacterium and Streptomyces) and in a small number of other bacteria. Beyond that: nothing. No plants. No animals. No archaea.
The implication is clean: ergothioneine synthesis is a fungal trait that originated in bacteria and was retained throughout fungal evolution. Every mushroom species that produces fruiting bodies — from shiitake to lion's mane to porcini — inherits this biosynthesis capacity from an ancestor that acquired it from a soil bacterium hundreds of millions of years ago.
The Bacterial Origin: How Fungi Acquired This Pathway
The fact that Egt1 appears in actinobacteria suggests that ergothioneine synthesis is far older than the fungal kingdom itself.
Actinobacteria are ancient organisms. They live in soil, form networks in the ground, and are among the most metabolically diverse bacteria on Earth. Streptomyces, one of the actinobacterial genera that carries the Egt1 gene, is also the source of most naturally occurring antibiotics discovered in the 20th century.
Horizontal gene transfer — the movement of genes between organisms that are not parent and offspring — is how microorganisms share useful metabolic tools across species and even across kingdoms. Jones and colleagues identified multiple independent horizontal transfer events in the evolutionary history of Egt1, consistent with actinobacteria transferring the gene to early fungal lineages on more than one occasion.[1]
Why would ergothioneine production be valuable enough to be preserved through these transfers? The leading hypothesis is that ergothioneine serves a protective function against oxidative damage in the organism that makes it. Fungi live in environments with high oxidative stress — soil, decaying wood, animal tissue — and a stable, non-auto-oxidizing antioxidant that concentrates in metabolically active areas would be a useful tool. Actinobacteria, living in similar environments, likely benefit from it for the same reason.
What is clear is that the evolutionary history of this pathway is ancient and specifically fungal-bacterial. The lineages that did not acquire it — plants, animals, and most other bacteria — do not have it today.
The Body's Response: A Dedicated Transporter for a Compound It Cannot Make
The human inability to synthesize ergothioneine doesn't mean we don't need it. It means we have to get it somewhere else.
The biological evidence that we need it comes from the OCTN1 transporter — technically called SLC22A4 — a membrane protein found in the intestinal lining, kidneys, and in especially high concentrations in tissues under oxidative stress: the liver, the brain, the eyes, and the mitochondria-dense cells of muscles and bone marrow.
Cheah, Halliwell, and colleagues reviewed the current state of ergothioneine research in a 2021 paper that covered the tissue distribution of OCTN1: it is concentrated precisely in the tissues that would benefit most from a stable antioxidant — tissues that process high volumes of oxygen and generate correspondingly high volumes of reactive oxygen species as a byproduct.[3]
The evolutionary argument is straightforward. SLC22A4 is strongly conserved across mammalian genomes, meaning natural selection preserved and refined it over time rather than allowing it to decay as unused genes typically do. An organism that maintained efficient ergothioneine absorption had a fitness advantage over one that didn't — consistently, over millions of generations. This selection happened against a backdrop where the only supply of ergothioneine was dietary, from fungi.
The co-evolutionary picture: fungi were part of the ancestral human diet (as they were part of every omnivore's diet), fungi contained ergothioneine, the ability to efficiently absorb ergothioneine was beneficial, and natural selection built and preserved dedicated absorption machinery for it.
A full examination of the OCTN1 mechanism, including what happens when the transporter is absent or mutated (associated with Crohn's disease risk), is at OCTN1: The Dedicated Transporter That Proves Ergothioneine Matters.
Which Mushrooms Deliver the Most Ergothioneine
If fungi are the only source, the practical question is which fungi deliver the most.
Kalaras, Beelman, and colleagues published the most comprehensive analysis of ergothioneine content across mushroom species in 2017 in Food Chemistry. Their team measured both ergothioneine and glutathione — another antioxidant — across a wide range of commonly available and specialty mushrooms.[2]
The ranking by ergothioneine content:
| Species | Common Name | EGT Relative Rank |
|---|---|---|
| Boletus edulis | Porcini | Highest |
| Pleurotus eryngii | King oyster | Second highest |
| Agaricus bisporus (portobello) | Portobello | Moderate |
| Pleurotus ostreatus | Oyster | Moderate |
| Lentinula edodes | Shiitake | Moderate-low |
| Agaricus bisporus (button) | White button | Lower end |
The gap between porcini and button mushrooms is substantial — porcini and king oyster mushrooms contain far higher ergothioneine concentrations than the white button mushrooms that account for most mushroom consumption in Western countries.[2]
Ergothioneine Content
Porcini Contains 24x More Ergothioneine Than White Button
Not all mushrooms are equal as ergothioneine sources. Kalaras et al. (2017) measured 13 species — porcini (king bolete) topped the ranking at 628 μg/g dry weight, roughly 10–100x any non-mushroom food. Bar length uses square-root scaling to show relative ordering without porcini dominating visually.
Porcini (Boletus edulis)
Oyster (Pleurotus ostreatus)
Shiitake (Lentinula edodes)
Portobello / Crimini (A. bisporus)
White button (A. bisporus)
Chanterelle (Cantharellus cibarius)
Why it matters: Humans have a dedicated cellular transporter (OCTN1/SLC22A4) for ergothioneine — suggesting the compound serves an ongoing physiological role rather than being incidental. Common grocery mushrooms still rank among the highest ergothioneine foods in the typical diet; porcini are exceptional but less widely available.
Source: Kalaras MD et al. (2017), Food Chemistry — “Mushrooms: A rich source of the antioxidants ergothioneine and glutathione.” Values are dry-weight concentrations; bars use square-root scaling to show relative differences without porcini collapsing the other species.
Kalaras's team also found that ergothioneine and glutathione co-occur in mushrooms at concentrations far exceeding any other food tested, and that the two antioxidants were strongly correlated across species. This co-occurrence is relevant because glutathione and ergothioneine appear to act on different oxidative targets through different mechanisms — each functioning as a complementary rather than a redundant defense.
One practical note: cooking reduces ergothioneine content less than it reduces most other antioxidants, because ergothioneine is unusually heat-stable. This means the ranking above applies broadly to cooked mushrooms as well as raw, though some loss does occur.
For a complete breakdown by species including less common varieties and cultivated vs. wild differences, see Ergothioneine Content by Mushroom Species: A Complete Ranking.
The Dietary Gap: What Happens in Low-Mushroom Populations
The populations with the highest mushroom consumption — Japan, Korea, several Mediterranean countries — also show up in some longevity research with better aging outcomes. The connection is correlational and involves many dietary factors. But ergothioneine is one specific candidate worth examining.
Biochemist Bruce Ames proposed in a 2018 paper in PNAS that ergothioneine belongs on a list of what he called longevity vitamins — a set of nutrients that aren't essential for preventing acute deficiency disease in the classical sense, but that the body requires for the long-term maintenance of cellular health and protection against aging-related damage.[4]
The conceptual framework Ames used is called the triage theory. The core idea is that when a nutrient is scarce, the body prioritizes using it for short-term survival functions over long-term maintenance. You don't develop visible deficiency symptoms immediately. But over years, the gradual shortage of a nutrient that your cells rely on for oxidative protection accumulates as cellular damage that eventually expresses as disease or functional decline.[4]
Applied to ergothioneine: the relevant question isn't whether low mushroom intake causes a diagnosable deficiency state. It's whether tissues that rely on OCTN1-supplied ergothioneine for protection are operating with lower antioxidant reserves in people who rarely eat mushrooms.
Cheah and colleagues noted in their 2021 review that plasma ergothioneine levels vary substantially across populations and correlate with mushroom intake patterns.[3] People in countries with high mushroom consumption have measurably higher circulating ergothioneine than people in low-mushroom-consumption countries.
The honest framing of where the evidence stands: the triage theory is a well-reasoned hypothesis supported by mechanistic data and epidemiological associations. It does not yet have clinical trial confirmation in the form of a randomized study showing that increasing mushroom intake reduces disease incidence. The hypothesis is compelling. It remains a hypothesis.
What is established: only fungi make ergothioneine, mushrooms are by far the richest dietary source, and the human body has evolved dedicated machinery to absorb it. Whether that combination adds up to a longevity argument is examined in more depth at Ergothioneine and Longevity: The Vitamin of Longevity Hypothesis.
The Bottom Line
Jones et al. (2014) mapped the ergothioneine biosynthesis gene across the tree of life and found it in fungi and some bacteria — nowhere in the animal or plant kingdoms. Fungi acquired this pathway from actinobacteria through horizontal gene transfer, and mushrooms became the primary dietary source for all organisms that eat them but cannot make ergothioneine themselves. Kalaras et al. (2017) established the practical ranking: porcini and king oyster mushrooms contain the highest concentrations, while the most commonly consumed Western mushroom (white button) falls considerably lower. The implication for populations with low mushroom intake is a hypothesis, not an established deficiency — but the biological infrastructure (a dedicated human transporter for a compound only fungi make) suggests the relationship is not accidental.
Frequently Asked Questions
Sources & References
- 1RTHM-00604·Jones, Gary W et al. (2014). “The evolutionary history of the genes involved in the biosynthesis of the antioxidant ergothioneine..” Gene.Study breakdown →PubMed →↩
- 2RTHM-00476·Kalaras, Michael D et al. (2017). “Mushrooms: A rich source of the antioxidants ergothioneine and glutathione..” Food chemistry.Study breakdown →PubMed →↩
- 3RTHM-00678·Cheah, Irwin K et al. (2021). “Ergothioneine, recent developments..” Redox biology.Study breakdown →PubMed →↩
- 4RTHM-00936·Ames, Bruce N (2018). “Prolonging healthy aging: Longevity vitamins and proteins..” Proceedings of the National Academy of Sciences of the United States of America.Study breakdown →PubMed →↩