Biosynthesis and Production of Statins by Filamentous Fungi

Statins are a class of fungal secondary metabolites that inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Filamentous fungi, notably Aspergillus terreus, Penicillium spp. and Monascus spp., naturally produce statins such as lovastatin and compactin via the mevalonate pathway. Central to their biosynthesis are modular polyketide synthases encoded within discrete gene clusters, often co-located with pathway regulators. Production platforms employ both submerged fermentation in liquid media and solid-state fermentation on agro-industrial wastes, enabling scale-up and cost efficiency. Strain improvement through classical mutagenesis, transcription factor engineering and medium optimisation has raised yields from milligram to gram-per-litre titres. Recent efforts extend the strain repertoire by exploring marine-derived isolates and integrating omics-guided promoter selection to boost statin gene cluster expression. The global significance of fungal statin bioprocessing encompasses pharmaceutical manufacture of cholesterol-lowering drugs, platforms for semi-synthetic derivatives and sustainable valorisation of biomass residues.

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Biosynthesis and Production of Statins by Filamentous Fungi publication trend

The graph below shows the total number of articles in biosynthesis and production of statins by filamentous fungi across all publications each year (not limited to Nature Index journals).

Technical terms

Statins: Polyketide-derived fungal metabolites that competitively inhibit HMG-CoA reductase to lower cholesterol synthesis.

HMG-CoA reductase: The enzyme catalysing the conversion of HMG-CoA to mevalonate, the rate-limiting step of the mevalonate pathway.

Polyketide synthase: A multi-domain enzyme complex responsible for iterative condensation of acyl units to form the statin backbone.

Biosynthetic gene cluster: A contiguous set of genes encoding enzymes, transporters and regulators required for secondary metabolite biosynthesis.

Solid-state fermentation: Cultivation of fungi on moist solid substrates without free-flowing water, used to enhance secondary metabolite yields and reduce effluent.

Submerged fermentation: Growth of fungi in liquid media under controlled aeration and agitation, enabling precise parameter control and scale-up.

References

1. Screening and genetic engineering of marine-derived Aspergillus terreus for high-efficient production of lovastatin. Microbial Cell Factories (2024).
2. Statins—From Fungi to Pharmacy. International Journal of Molecular Sciences (2023).
3. Exploitation of Sugarcane Bagasse and Environmentally Sustainable Production, Purification, Characterization, and Application of Lovastatin by Aspergillus terreus AUMC 15760 under Solid-State Conditions. Molecules (2023).