Biosynthetic Pathways of Antifungal Echinocandins

The echinocandins are a class of cyclic lipohexapeptides produced by filamentous fungi that serve as potent inhibitors of fungal cell wall synthesis. Biosynthesis relies on large multienzyme complexes: nonribosomal peptide synthetases (NRPSs) assemble the peptide core from amino acid building blocks, while polyketide synthases (PKSs) and tailoring enzymes such as cytochrome P450 monooxygenases introduce specific lipid side chains and hydroxylations. The entirety of biosynthetic machinery is typically encoded in contiguous gene clusters, enabling coordinated regulation of peptide assembly, modification and secretion. Semisynthetic modification of natural echinocandins—for example pneumocandin B0—yield clinically approved antifungals such as caspofungin, micafungin and anidulafungin. Advances in genomics have revealed interspecies variations in cluster architecture, shedding light on structural diversity and informing the design of novel derivatives with improved pharmacological properties. Metabolic engineering and fermentation strategies further enhance precursor supply and product yields, underpinning scalable production for global therapeutic use.

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Biosynthetic Pathways of Antifungal Echinocandins publication trend

The graph below shows the total number of articles in biosynthetic pathways of antifungal echinocandins across all publications each year (not limited to Nature Index journals).

Technical terms

Echinocandins: cyclic lipohexapeptide antifungal agents that inhibit fungal cell wall β-1,3-glucan synthesis.

Nonribosomal peptide synthetase (NRPS): a multimodular enzyme complex that assembles peptides from amino acids independent of ribosomes.

Polyketide synthase (PKS): a multidomain enzyme responsible for the biosynthesis of polyketide backbones through successive condensations of acyl-CoA precursors.

β-1,3-Glucan synthase: membrane-bound enzyme complex that catalyses the polymerisation of β-1,3-glucan, a key structural component of fungal cell walls.

Cytochrome P450 monooxygenase: a heme-containing enzyme that introduces oxygen atoms into organic substrates, mediating hydroxylation and other modifications.

References

1. Effect of fatty acids on intracellular pneumocandin B0 storage in the fermentation of Glarea lozoyensis. Bioresources and Bioprocessing (2023).
2. Improving the production of the micafungin precursor FR901379 in an industrial production strain. Microbial Cell Factories (2023).
3. Echinocandins: structural diversity, biosynthesis, and development of antimycotics. Applied Microbiology and Biotechnology (2020).
4. Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis. BMC Genomics (2013).