Biosynthetic Mechanisms of Fungal Natural Products
Summary
Fungi deploy an extraordinary array of enzymatic strategies to construct structurally diverse natural products, including polyketides, nonribosomal peptides, terpenoids and biaryl dimers. Central to these pathways are multi‐domain polyketide synthases (PKSs) and nonribosomal peptide synthases (NRPSs) that assemble complex carbon frameworks from simple acyl‐ and amino‐acid precursors. Tailoring enzymes such as cytochrome P450 monooxygenases, Baeyer–Villiger monooxygenases and methyltransferases introduce oxidation, rearrangement and functional-group modifications that define bioactivity. Biosynthetic genes are typically arranged in contiguous clusters under coordinated regulatory control, facilitating coordinated expression and enabling heterologous expression in amenable hosts. Advances in genome mining, comparative bioinformatics and structural biology have uncovered previously cryptic pathways and elucidated catalytic mechanisms of key enzymes, including those mediating stereoselective dimerisation. The global significance of fungal natural products spans pharmaceuticals (antibiotics, anticancer agents), agriculture (biopesticides, herbicides), industrial pigments and emerging materials such as natural semiconductors. Understanding these biosynthetic frameworks underpins sustainable production and guided pathway engineering for novel compound discovery.
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Biosynthetic Mechanisms of Fungal Natural Products publication trend
The graph below shows the total number of articles in biosynthetic mechanisms of fungal natural products across all publications each year (not limited to Nature Index journals).
Technical terms
Polyketide synthase (PKS): Multi-domain enzyme that assembles polyketide backbones via iterative condensation of acyl-CoA units.
Nonribosomal peptide synthase (NRPS): Multi-enzyme complex catalysing ribosome-independent assembly of peptide natural products from activated amino acids.
Cytochrome P450 monooxygenase: Heme-containing oxidase that introduces oxygen functionalities, often critical for compound diversification.
Baeyer–Villiger monooxygenase: Flavin-dependent enzyme inserting an oxygen atom into ketones to form lactones or ring-expanded products.
Biosynthetic gene cluster: Contiguous set of co-regulated genes encoding all enzymes and regulators required for a specific natural product pathway.
References
- The ‘emodin family’ of fungal natural products–amalgamating a century of research with recent genomics-based advances. Natural Product Reports (2023).
- Production of the antifungal biopesticide physcion through the combination of microbial fermentation and chemical post-treatment. Bioresources and Bioprocessing (2023).
- The fungal gene cluster for biosynthesis of the antibacterial agent viriditoxin. Fungal Biology and Biotechnology (2019).
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