Keywords
HMG-CoA reductase inhibitors
microbial fermentation
chemoenzymatic synthesis
process intensification
metabolic engineering
green chemistry
Abstract
This review critically evaluates industrial strategies for statin production, with a focus on biotechnological, chemical, and chemoenzymatic approaches to HMG-CoA reductase inhibitors. Microbial fermentation remains the dominant platform for producing natural statins such as lovastatin, offering scalable and robust manufacturing routes. Semi-synthetic derivatives (e.g., simvastatin and pravastatin) are obtained through selective chemical or enzymatic modifications that enhance pharmacokinetic properties. In contrast, fully synthetic statins, including atorvastatin and rosuvastatin, rely on multi-step asymmetric synthesis, enabling precise structural control at the cost of increased process complexity and environmental burden. Comparative analysis highlights the potential of chemoenzymatic strategies that combine fermentation-derived intermediates with biocatalytic transformations to improve selectivity, yield, and overall process efficiency. Process intensification technologies, including continuous fermentation, immobilized biocatalysts, and flow chemistry, also contribute to reduced solvent consumption and improved sustainability. Advances in metabolic engineering, particularly CRISPR/Cas-based strain optimization and synthetic microbial systems, enhance precursor supply and product formation. Despite these developments, challenges related to scalability, regulatory constraints, and environmental impact remain significant. Integrated hybrid approaches appear to offer the most balanced strategy by combining efficiency, scalability, and sustainability within modern statin manufacturing systems.
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