Bioactive Fungal Metabolites in Cancer Therapeutics

Fungi are prolific producers of chemically diverse secondary metabolites, many of which possess potent anticancer activities. These small molecules, including polyketides, terpenoids and non-ribosomal peptides, act on multiple cellular targets to inhibit tumour growth, induce programmed cell death and modulate the tumour microenvironment. A prominent example is terrein, a cyclopentenone derivative from Aspergillus terreus, which has been shown to interfere with proteasome function, suppress inflammatory signalling and enhance the efficacy of established chemotherapeutics. Other fungal metabolites under investigation include the proteasome inhibitor marizomib, cyclic peptides that disrupt microtubule dynamics and lectin-like proteins that engage immune receptors. Together, these compounds illustrate the capacity of fungi to furnish novel scaffolds that address resistance mechanisms and selective toxicity towards cancer cells.

Advances in fermentation technology, genetic engineering of biosynthetic gene clusters and co-culture methods have expanded the pipeline of fungal leads. High-throughput screening combined with metabolomic profiling accelerates the identification of active fractions, while structural optimisation and formulation strategies are refining pharmacokinetics and target specificity. The global significance of these efforts is underscored by the need for new therapies against refractory malignancies and the potential for cost-effective production in low-resource settings. Beyond direct cytotoxicity, certain fungal metabolites also exhibit immunomodulatory and anti-angiogenic properties, supporting combination regimens that integrate conventional chemotherapy, targeted agents and immunotherapy.

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Bioactive Fungal Metabolites in Cancer Therapeutics publication trend

The graph below shows the total number of articles in bioactive fungal metabolites in cancer therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Secondary metabolite: A low-molecular-weight compound not directly involved in growth or reproduction but often mediating ecological interactions and bioactivity.

Proteasome: A multicatalytic protease complex responsible for regulated degradation of intracellular proteins, critical for cell cycle control and apoptosis.

Hypoxia: A state of reduced oxygen availability in tissues that influences tumour metabolism, drug response and resistance.

Apoptosis: Programmed cell death characterised by caspase activation, DNA fragmentation and membrane blebbing, often targeted by anticancer agents.

Chemomodulation: Enhancement or alteration of a drug’s efficacy or toxicity profile by a secondary agent, typically through complementary molecular mechanisms.

References

1. Chemomodulatory Effect of the Marine-Derived Metabolite “Terrein” on the Anticancer Properties of Gemcitabine in Colorectal Cancer Cells. Marine Drugs (2023).
2. Large-Scale Production of Bioactive Terrein by Aspergillus terreus Strain S020 Isolated from the Saudi Coast of the Red Sea. Biomolecules (2019).
3. Studies on terrein as a new class of proteasome inhibitors. Journal of the Brazilian Chemical Society (2010).