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Microbial production and biomedical applications of lovastatin.

Seenivasan A, Subhagar S, Aravindan R, Viruthagiri T - Indian J Pharm Sci (2008)

Bottom Line: Lovastatin acts by competitively inhibiting the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase involved in the biosynthesis of cholesterol.Production of lovastatin by fermentation decreases the production cost compared to costs of chemical synthesis.This review deals with the structure, biosynthesis, various modes of fermentation and applications of lovastatin.

View Article: PubMed Central - PubMed

Affiliation: Biochemical Engineering Laboratory, Department of Chemical Engineering, Annamalai University, Annamalai Nagar-608 002, India.

ABSTRACT
Lovastatin is a potent hypercholesterolemic drug used for lowering blood cholesterol. Lovastatin acts by competitively inhibiting the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase involved in the biosynthesis of cholesterol. Commercially lovastatin is produced by a variety of filamentous fungi including Penicillium species, Monascus ruber and Aspergillus terreus as a secondary metabolite. Production of lovastatin by fermentation decreases the production cost compared to costs of chemical synthesis. In recent years, lovastatin has also been reported as a potential therapeutic agent for the treatment of various types of tumors and also play a tremendous role in the regulation of the inflammatory and immune response, coagulation process, bone turnover, neovascularization, vascular tone, and arterial pressure. This review deals with the structure, biosynthesis, various modes of fermentation and applications of lovastatin.

No MeSH data available.


Related in: MedlinePlus

Role of lovastatin in inhibition of cholesterol synthesis The cellular and molecular mechanism of statins by considering the biosynthetic pathway of cholesterol. The main step leading to the reduction in cholesterol synthesis is the decrease in the precursor mevalonate by the inhibition of the HMG-CoA reductase. By inhibiting the HMG-CoA to mevalonate, the biosynthesis of two major downstream products of mevalonate, cholesterol production and synthesis of isoprenoids are influenced.
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Figure 0001: Role of lovastatin in inhibition of cholesterol synthesis The cellular and molecular mechanism of statins by considering the biosynthetic pathway of cholesterol. The main step leading to the reduction in cholesterol synthesis is the decrease in the precursor mevalonate by the inhibition of the HMG-CoA reductase. By inhibiting the HMG-CoA to mevalonate, the biosynthesis of two major downstream products of mevalonate, cholesterol production and synthesis of isoprenoids are influenced.

Mentions: Lovastatin is an effective inhibitor of the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (mevalonate: NADP1 oxidoreductase, EC 1.1.1.34) that catalyzes the reduction of HMG-CoA to mevalonate during synthesis of cholesterol1. When the lactone ring of lovastatin is in its open form, as it would be in the human liver, the structure bears a strong similarity to HMG-CoA. It has been shown that lovastatin and the other monacolins are very specific competitive inhibitors of the reductase2–5, which reduce serum cholesterol levels by blocking cholesterol biosynthesis as shown in the fig. 1. An attractive characteristic of these inhibitors is that they selectively reduce levels of low-density-lipoprotein (LDL), the bad lipoproteins. While levels of high-density lipoprotein (HDL, the good lipoproteins) remain unaffected, or in some cases, even increase. Lovastatin is currently made commercial by fermentation. However, other synthetic routes have also been considered. One of the reported routes is by a cell-free extraction in aqueous solution, where the lactone ring is in its open form6. Another method involves the use of silyl ethers7.


Microbial production and biomedical applications of lovastatin.

Seenivasan A, Subhagar S, Aravindan R, Viruthagiri T - Indian J Pharm Sci (2008)

Role of lovastatin in inhibition of cholesterol synthesis The cellular and molecular mechanism of statins by considering the biosynthetic pathway of cholesterol. The main step leading to the reduction in cholesterol synthesis is the decrease in the precursor mevalonate by the inhibition of the HMG-CoA reductase. By inhibiting the HMG-CoA to mevalonate, the biosynthesis of two major downstream products of mevalonate, cholesterol production and synthesis of isoprenoids are influenced.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3040861&req=5

Figure 0001: Role of lovastatin in inhibition of cholesterol synthesis The cellular and molecular mechanism of statins by considering the biosynthetic pathway of cholesterol. The main step leading to the reduction in cholesterol synthesis is the decrease in the precursor mevalonate by the inhibition of the HMG-CoA reductase. By inhibiting the HMG-CoA to mevalonate, the biosynthesis of two major downstream products of mevalonate, cholesterol production and synthesis of isoprenoids are influenced.
Mentions: Lovastatin is an effective inhibitor of the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (mevalonate: NADP1 oxidoreductase, EC 1.1.1.34) that catalyzes the reduction of HMG-CoA to mevalonate during synthesis of cholesterol1. When the lactone ring of lovastatin is in its open form, as it would be in the human liver, the structure bears a strong similarity to HMG-CoA. It has been shown that lovastatin and the other monacolins are very specific competitive inhibitors of the reductase2–5, which reduce serum cholesterol levels by blocking cholesterol biosynthesis as shown in the fig. 1. An attractive characteristic of these inhibitors is that they selectively reduce levels of low-density-lipoprotein (LDL), the bad lipoproteins. While levels of high-density lipoprotein (HDL, the good lipoproteins) remain unaffected, or in some cases, even increase. Lovastatin is currently made commercial by fermentation. However, other synthetic routes have also been considered. One of the reported routes is by a cell-free extraction in aqueous solution, where the lactone ring is in its open form6. Another method involves the use of silyl ethers7.

Bottom Line: Lovastatin acts by competitively inhibiting the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase involved in the biosynthesis of cholesterol.Production of lovastatin by fermentation decreases the production cost compared to costs of chemical synthesis.This review deals with the structure, biosynthesis, various modes of fermentation and applications of lovastatin.

View Article: PubMed Central - PubMed

Affiliation: Biochemical Engineering Laboratory, Department of Chemical Engineering, Annamalai University, Annamalai Nagar-608 002, India.

ABSTRACT
Lovastatin is a potent hypercholesterolemic drug used for lowering blood cholesterol. Lovastatin acts by competitively inhibiting the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase involved in the biosynthesis of cholesterol. Commercially lovastatin is produced by a variety of filamentous fungi including Penicillium species, Monascus ruber and Aspergillus terreus as a secondary metabolite. Production of lovastatin by fermentation decreases the production cost compared to costs of chemical synthesis. In recent years, lovastatin has also been reported as a potential therapeutic agent for the treatment of various types of tumors and also play a tremendous role in the regulation of the inflammatory and immune response, coagulation process, bone turnover, neovascularization, vascular tone, and arterial pressure. This review deals with the structure, biosynthesis, various modes of fermentation and applications of lovastatin.

No MeSH data available.


Related in: MedlinePlus