Mushroom Metabolomics & Secondary Metabolites
907 new compounds
In 2024, researchers cataloged 907 novel fungal-derived compounds, a 64% increase over 2023, driven by metabolomics-guided discovery and biosynthetic pathway engineering.
Bao et al., Mycology, 2025
8 methods
used to identify 3 new hericenones from Lion's Mane in a single 2025 study: HR-MS, NMR, CD spectroscopy, and synthesis
Silent clusters
Lion's Mane genome contains unexpressed biosynthetic gene clusters that may produce entirely undiscovered compounds
153%
increase in terpenoid compound discoveries in 2024 versus 2023, driven by metabolomics-guided platforms
Bao et al., Mycology, 2025
View as image ↗In 2024, researchers cataloged 907 novel compounds derived from fungi, a 64% increase over the 553 new fungal compounds discovered in 2023.[11][10] Among those 907 compounds, 362 were terpenoids, a 153% increase over the prior year. This acceleration is not random. It is the direct result of a specific suite of modern analytical, genomic, and computational tools that have transformed what chemists can find in a mushroom.
The compounds that make medicinal mushrooms biologically active are far more numerous than the beta-glucan polysaccharides that dominate supplement marketing. Adejor and colleagues' 2025 FEMS Microbiology Reviews paper makes the methodological case: metabolomics has transformed fungal biology from a descriptive science (what is in this mushroom?) into a predictive one (what should this mushroom be able to produce, and under what conditions?).[1] This article explains the toolkit making that transformation possible, with a concrete mushroom story for each method. For context on what secondary metabolites are and why they matter beyond polysaccharides, see Secondary Metabolites in Mushrooms: The Compounds Beyond Polysaccharides and the mycology fundamentals guide.
Key Takeaways
- Bao et al. 2025 cataloged 907 novel fungal-derived compounds from 2024 publications, a 64% increase over 2023, including 362 terpenoids (153% increase); the acceleration is driven by metabolomics-guided discovery and biosynthetic pathway engineering.
- Wang et al. 2025 used 8 complementary analytical methods (high-resolution mass spectrometry, NMR, circular dichroism, synthetic confirmation, and others) to identify 3 entirely new hericenone structures in Lion's Mane that single-method approaches had missed.
- Randeni et al. 2025 combined LC-MS compound identification with network pharmacology and molecular docking to map Chaga's anti-diabetic mechanisms from chemistry to molecular target, exemplifying the chemistry-to-mechanism pipeline.
- Windsor et al. 2025 compared commercial Chaga supplements using multiple analytical techniques and found enormous variation in compound profiles between products, showing that the same mushroom label can represent chemically very different products.
- Chen et al. 2017 sequenced the Lion's Mane genome and found multiple biosynthetic gene clusters for terpenoids and polyketides that are only expressed under specific conditions, meaning much of the mushroom's chemical potential is "silent" and undiscovered under standard lab conditions.
- Wang et al. 2023 reviewed how CRISPR/Cas tools are being used to activate these silent biosynthetic gene clusters, enabling directed biosynthesis of novel compounds and increased yields of known ones.
How Many New Mushroom Compounds Are Being Discovered?
The scale of what is being found is striking. Shi and colleagues' 2024 review cataloged all novel bioactive secondary metabolites from fungi published in 2023: 553 new compounds, including 219 polyketides, 145 terpenoids, 35 steroids, 106 alkaloids, and 48 peptides.[10] Each of these compounds was confirmed as new to science in that year alone.
The following year's count from Bao and colleagues was 907 compounds, with the terpenoid category specifically growing 153% year-over-year.[11] Bao and colleagues attribute this acceleration to two specific drivers: metabolomics-guided discovery platforms that systematically screen for new compound signatures, and biosynthetic pathway engineering that activates previously silent compound-producing genes.
For context, a single well-studied medicinal mushroom can contain thousands of small molecules. The 907 new compounds in 2024 represent discoveries across all fungi, but even a fraction of that in a single species is remarkable when you consider that most mushroom supplements are sold and labeled based on one or two compound classes (beta-glucans, polysaccharides) out of hundreds or thousands present.
Adejor and colleagues' 2025 FEMS review provides the broader framing: the reason discovery is accelerating is that metabolomics shifted the question researchers ask.[1] Older targeted approaches asked: "how much ergothioneine is in this mushroom?" Untargeted metabolomics asks: "what is every compound in this mushroom, and which ones have we never seen before?" The second approach finds new compounds by definition.
The Multi-Method Case Study: How Three New Lion's Mane Compounds Were Found
Wang and colleagues' 2025 paper in the Journal of Natural Products is a detailed story of how new mushroom compounds are discovered in practice, and it illustrates why no single analytical method is sufficient.[2] The team was working with Lion's Mane (Hericium erinaceus) fruiting bodies, specifically looking at the hericenone family of aromatic compounds. They identified 3 new hericenone structures that previous studies had missed.
The method count tells the story: 8 complementary analytical techniques were used. High-resolution mass spectrometry (HR-MS) gave each compound's molecular formula and mass. Nuclear magnetic resonance spectroscopy (NMR) determined the three-dimensional arrangement of atoms in the molecule, because two compounds with the same mass can have completely different structures. Circular dichroism (CD) spectroscopy established the three-dimensional handedness (chirality) of the molecules, because the left-handed and right-handed versions of the same molecule can have very different biological activities. Synthetic confirmation (making the compound in the lab and verifying it matches the natural sample) provided the final proof.
Why did it take 8 methods to find 3 compounds that had been missed? Because each method has a limit. Mass spectrometry distinguishes compounds by mass but cannot determine 3D structure. NMR determines structure but requires more material and time. CD spectroscopy establishes chirality that NMR alone cannot always resolve. When several techniques are used simultaneously, each fills a gap the others leave.
This is why the rate of new discovery is accelerating: not because mushrooms have changed, but because the instruments available to analyze them have become more sensitive, more specific, and more routinely combined. A compound that was invisible to 1991 HPLC methods is detectable by 2025 HR-MS.
LC-MS and Network Pharmacology: From Compound to Mechanism
Identifying a new compound is only the first step. Understanding what it does biologically requires a second layer of analysis, and the Randeni et al. 2025 study on Chaga illustrates how that pipeline now works.[3]
The study used LC-MS (liquid chromatography coupled with mass spectrometry) to characterize the compounds in Chaga (Inonotus obliquus) extracts, then fed those identified compounds into network pharmacology analysis. Network pharmacology uses databases of known protein targets to predict which proteins each compound is likely to interact with, based on structural similarity to known ligands. The Randeni team then used molecular docking to simulate how each compound physically fits into candidate protein binding sites, providing a computational confirmation of the target interaction.
The result: a pathway from chemistry (what compounds are in Chaga?) to mechanism (which proteins do those compounds interact with, and through which biological pathways do those interactions explain Chaga's anti-diabetic activity?). This pipeline (LC-MS to network pharmacology to molecular docking) did not exist in its current form a decade ago. It now enables researchers to generate mechanistic hypotheses about new compounds without waiting for expensive in vivo experiments to confirm each one.
The same analytical approach also exposed a consumer-relevant problem. Windsor and colleagues' 2025 comparative study of commercial Chaga supplement products found enormous variation in compound profiles between products using the same mushroom name and claiming similar specifications.[4] Modern analytical chemistry can now demonstrate that "Chaga supplement" is not a chemically specific category. The same name covers products that are chemically quite different. For more on how growing conditions and extraction affect compound profiles, see How Growing Substrate Affects Mushroom Bioactive Content and Do Fruiting Bodies Have More Bioactive Compounds Than Mycelium?.
Genomic Mining: Reading the Chemistry From the DNA
The analytical chemistry approach finds compounds that are actually present. But some of the most interesting mushroom chemistry is not present in any sample collected under normal conditions. It exists as potential, encoded in the genome but never expressed.
Chen and colleagues' 2017 study sequenced the full genome and transcriptome (the map of which genes are actively being expressed) of Lion's Mane.[6] The genomic analysis revealed multiple biosynthetic gene clusters (BGCs), groups of co-located genes that together code for producing a single class of compound. The specific finding: many of these clusters were present in the genome but not being expressed under the conditions the mushroom was grown. They were silent.
This is a profound insight. It means that what analytical chemistry finds in a standard Lion's Mane extract is not the same as what Lion's Mane is chemically capable of producing. The mushroom might produce additional terpenoids or polyketides under different conditions (specific nutrients, environmental stress, competing organisms) that have never been isolated and characterized because no one has triggered the expression of those genes.
The genomic approach can predict these compounds before they are isolated, simply by identifying the genes and comparing them to known BGC sequences. When a BGC resembles the genes for a known compound class, the mushroom is likely making a related compound under the right conditions.
Tarafder and colleagues' 2024 review of advances in mushroom genetic studies documents the full current toolkit: genome sequencing, transcriptomics, CRISPR editing, and the integration of multi-omics platforms for compound discovery.[8] The transition from morphological taxonomy (what does the mushroom look like?) to genomic characterization (what can it produce?) is one of the core shifts driving the compound discovery acceleration.
There is also an evolutionary wrinkle. Reynolds and colleagues established in 2018 that fungi can acquire entire biosynthetic gene clusters from other species through horizontal gene transfer, with the psilocybin gene cluster appearing in taxonomically unrelated genera being the most dramatic example.[7] This means compound profiles cannot always be predicted from taxonomy alone. A mushroom may produce a compound class associated with a completely different fungal lineage if it acquired that cluster via gene transfer.
Directing the Chemistry: CRISPR and Silent Gene Activation
The next step after finding silent gene clusters is activating them. Wang and colleagues' 2023 review covers how CRISPR/Cas genome editing tools are being applied to this problem in fungi.[5] CRISPR has been widely publicized in the context of gene therapy in humans. For fungi, its most immediately useful application is different: switching on biosynthetic gene clusters that are present but not active under standard culture conditions.
When researchers identify a silent BGC predicted to produce a novel compound, they can use CRISPR to modify the regulatory elements controlling that cluster, essentially forcing the fungus to express it. The result is production of a compound that the mushroom contains the instructions to make but would never make under normal conditions.
This shifts compound discovery from a purely analytical exercise (finding what is there) to a directed one (producing what should be there according to the genome). For compounds like terpenoids that are difficult to synthesize chemically, accessing them through activated fungal biosynthesis may be the most practical route to producing them in quantities sufficient for biological testing.
Kuang and colleagues' 2021 review of terpenoid diversity in just one medicinal mushroom species (Antrodia camphorata) shows why this matters.[9] A single species contains multiple classes of lanostane-type triterpenoids, ergostane-type triterpenoids, sesquiterpenes, and other terpenoid variants, each with distinct biological properties. Identifying all of these from natural samples takes years of collection and analysis. Directed biosynthesis could accelerate access to structurally related compounds that exist as genomic potential but not yet as isolated natural products.
What This Means for Medicinal Mushroom Science
The ergothioneine story illustrates how the tools connect. Yang and colleagues' 2020 research mapped the complete biosynthetic pathway for ergothioneine in enoki mushroom (Flammulina velutipes), identifying the key enzyme (EgtB) responsible for creating the unusual sulfur-histidine bond that makes ergothioneine structurally and biologically unique.[12] Knowing the enzyme means researchers can now study where and when the pathway is most active across mushroom species, identify genetic variation in EgtB that might explain differences in ergothioneine content between strains, and potentially engineer increased ergothioneine production by overexpressing the key enzymatic step.
This is the arc that modern chemistry is tracing for every important mushroom compound: from identification (mass spectrometry), to structure (NMR), to mechanism (network pharmacology), to genetic basis (genomics), to directed production (CRISPR and strain engineering).
The 907 compounds cataloged in 2024 exist within this broader picture.[11] Most will take years to be characterized biologically. Some will turn out to be inactive or toxic at relevant concentrations. A few will prove to have significant biological activities worth developing further. The acceleration in discovery is real; the clinical translation timeline is long. But the tools now exist to move from mushroom genome to compound structure to biological mechanism faster than was possible even five years ago.
For more on how AI and machine learning are extending this toolkit further, see AI-Driven Mushroom Compound Discovery: The Future of Mycochemistry. For the specific method of mass spectrometry in more depth, see Mushroom Metabolomics: How Mass Spectrometry Is Revealing New Compounds.
The Bottom Line
Modern chemistry is finding new mushroom compounds at an accelerating rate: 553 novel fungal compounds in 2023, 907 in 2024. The tools driving this include multi-method analytical chemistry (Wang 2025 found 3 new Lion's Mane hericenones using 8 instruments), LC-MS combined with network pharmacology (Randeni 2025 mapped Chaga's anti-diabetic mechanisms from compound to target), genomic mining (Chen 2017 found silent biosynthetic gene clusters in Lion's Mane producing compounds never yet isolated), and CRISPR activation of those silent clusters (Wang 2023). Each tool adds a layer: what compounds exist, what their structures are, what they do, and how to produce more of them.
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- 7RTHM-01000·Reynolds, Hannah T et al. (2018). “Horizontal gene cluster transfer increased hallucinogenic mushroom diversity..” Evolution letters.Study breakdown →PubMed →↩
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