Biotechnological production of statins: metabolic aspects and genetic approaches.

Statins are a class of drugs used for people with abnormal lipid levels (hyperlipidemia) that are among the best-selling medications in the United States. Thus, the biotechnological production of these drugs is of extreme importance for the pharmaceutical industry. Herein, we provide a non-exhaustive review of fungal species used to produce statin and highlighted the major factors affecting the efficacy of this process. The current biotechnological approaches and the advances of metabolic engineer to improve statins production by fungi are also emphasised. The biotechnological production of the main statins (lovastatin, pravastatin and simvastatin) use different species of filamentous fungi, among them Aspergillus terreus. The statins production is influenced by different types of nutrients available in the medium such as the carbon and nitrogen sources, and several researches have focused their efforts to find the optimal cultivation conditions. Enzymes belonging to Lov class, play essential roles in statin production and have been targeted to genetic manipulations in order to improve the efficiency for Lovastatin and Simvastatin production. For instance, Escherichia coli strains expressing the LovD have been successfully used for lovastatin production. Other examples of include the use of iRNA targeting LovF of A. terreus. Therefore, the fungi are important allies in the fight against hyperlipidemias. Although many studies have been conducted, investigations on bioprocess optimization (using both native or genetic-modified strains) are necessary.