How Fungi Are Reshaping Drug Discovery: 907 Novel Compounds Described in 2024
- jiaxin chen
- Sep 9
- 4 min read
Too long to read? Go for the highlights below.
Record discoveries: Researchers catalogued 907 novel fungal compounds in 2024—a 64% increase from 2023, with over half showing measurable pharmacological activity
Marine advantage: Plant-associated (38%)
and marine-derived fungi (30%) dominated discoveries, with deep-sea strains producing compounds that outperform existing clinical drugs
Commercial convergence: Biotechnology firms are combining traditional isolation methods with AI platforms to bridge the gap between laboratory discoveries and therapeutic applications
Beneath the forest floor and in the depths of our oceans, an extraordinary pharmaceutical treasure hunt is unfolding. According to a comprehensive review published in Mycology: An International Journal on Fungal Biology by researchers from the Chinese Academy of Sciences, investigators catalogued 907 novel compounds derived from fungi in 2024 alone—a 64% increase from the previous year's discoveries. This surge reflects not merely scientific enthusiasm, but the recognition that fungi represent one of nature's most sophisticated chemical factories.
The numbers tell a remarkable story. Of these 907 newly identified compounds, terpenoids dominated with 362 discoveries, followed by 284 polyketides and 108 alkaloids. Yet quantity alone fails to capture the true significance of this research. More than half of these compounds—475 in total—demonstrated measurable pharmacological activity, suggesting that fungi continue to harbour untapped therapeutic potential.
Marine Depths and Forest Canopies
The geographic distribution of these discoveries reveals where researchers are finding the most promising leads. Plant-associated fungi accounted for 38% of novel compounds, whilst marine-derived strains contributed 30%. This pattern suggests that fungi living in symbiotic relationships or extreme environments may be under greater evolutionary pressure to produce complex bioactive molecules.
Consider the marine fungus Aspergillus ustus, which produced carnemycin I—a compound demonstrating superior antibacterial activity against Ralstonia solanacearum compared to chloramphenicol. Similarly, the deep-sea strain Pseudallescheria boydii yielded compounds with antifungal properties surpassing amphotericin B, a clinical mainstay for serious fungal infections.
The Limits of Traditional Methods
Despite these successes, the research reveals persistent challenges. Traditional isolation techniques, whilst still dominant, account for declining proportions of new discoveries. The complexity and trace quantities of bioactive metabolites continue to present formidable obstacles. As the authors note, "key barriers include computational resource limitations for AI-based BGC prediction, specialised training needs for CRISPR-mediated activation and high costs of synthetic biology workflows."
This reality has prompted researchers to explore alternative approaches. Co-cultivation strategies, where different fungal species are grown together, have yielded compounds that neither species produces in isolation. The study documents how Alternaria brassicicola cultured with Penicillium granulatum produced novel bicyclic lactones not observed in monocultures.
Technological Convergence
The integration of genomics with natural product chemistry represents perhaps the most significant methodological advance. Molecular networking techniques now allow researchers to identify relationships between compounds before they are fully characterised. This approach guided the discovery of compounds such as gymnoasin A, which demonstrated significant inhibition of the NLRP3 inflammasome—a therapeutic target for conditions including Alzheimer's disease and Parkinson's disease.
Genome mining, meanwhile, enables researchers to predict the chemical capabilities of fungi by analysing their DNA. This technique led to the identification of triorsellinaldehyde from Aspergillus nidulans through targeted transcription factor engineering, effectively awakening a previously silent biosynthetic pathway.
Clinical Promise and Practical Challenges
The therapeutic potential extends across multiple disease areas. Anti-inflammatory compounds dominated the bioactivity profiles, with terpenoids showing particular promise in this category. Compound 292, isolated from Penicillium herquei, demonstrated anti-inflammatory activity superior to dexamethasone.
Antifungal activity represented another significant category, with polyketides frequently exhibiting potent effects. Notably, several compounds demonstrated activity against drug-resistant strains, addressing a growing clinical concern as resistance to existing antifungal agents increases.
Yet the path from laboratory bench to pharmacy shelf remains fraught. The structural complexity of fungal metabolites often renders them unsuitable for traditional drug development approaches. Manufacturing challenges, regulatory hurdles, and the need for extensive safety testing mean that few of these compounds will reach clinical application in their native form.
Bridging Discovery and Development
The research suggests that whilst traditional methods remain important, the future lies in hybrid approaches combining classical isolation techniques with modern genomic tools. This convergence is attracting commercial interest, with biotechnology firms recognising the untapped potential in fungal chemistry.
Novogaia, a startup focused on fungal-derived drug discovery, exemplifies this emerging approach. The company combines natural product expertise with artificial intelligence platforms for molecular property and structure prediction, enabling rapid evaluation of fungal compounds—even those that are extremely rare or chemically unusual. As the firm notes, this represents "a way of seeing 'around corners' in chemical space that others miss."
The company's rationale reflects a broader industry recognition: many serious diseases still lack effective treatments, yet fungi remain one of nature's richest sources of bioactive molecules. The historical precedent is compelling—fungi have already produced transformative medicines including statins, penicillin, and cyclosporine. Their unusual chemistry may be precisely what is needed for diseases that resist conventional therapeutic approaches.
Marine environments appear particularly promising, with fungi from extreme habitats producing compounds with novel mechanisms of action. The Mariana Trench-associated Aspergillus species, for instance, yielded compounds with unprecedented structural features that may translate into entirely new therapeutic approaches.
A Sustainable Outlook
The 64% increase in compound discovery reflects not only improved methodologies but also the vast, largely untapped diversity of fungal chemistry. However, the challenge lies in translating laboratory discoveries into clinical realities. Companies like Novogaia aim to bridge this gap by building partnerships across pharmaceutical and academic sectors, seeking to transform fungal molecules into first-in-class medicines.
The data from 2024 demonstrates that fungi continue to surprise researchers with their chemical ingenuity. As computational tools become more sophisticated and synthetic biology techniques more accessible, the rate of discovery may accelerate further. The true measure of success will not be in the number of compounds discovered, but in their translation into treatments that address unmet medical needs.
This quiet revolution in fungal chemistry suggests that nature's most prolific chemists—operating in the shadows of more charismatic organisms—may hold keys to addressing some of medicine's most pressing challenges. The question is no longer whether fungi can contribute to drug discovery, but how quickly commercial and academic partnerships can unlock their full therapeutic potential.
