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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

Structure of lovastatin All statins possess a common structure, a hexahydro-naphthalene system and a ß-hydroxylactone; their differences are due to side chains (R1) and methyl groups (R2) around the ring.
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Figure 0002: Structure of lovastatin All statins possess a common structure, a hexahydro-naphthalene system and a ß-hydroxylactone; their differences are due to side chains (R1) and methyl groups (R2) around the ring.

Mentions: Lovastatin (or mevinolin, monacolin K, and Mevacor, Merck) contains a methylbutyric side chain (R1) and a 6-α methyl group (R2) as shown in fig. 2. The foremost query addressed was whether a reduction in plasma cholesterol level with lovastatin would be associated with a reduction in the whole body production rate of cholesterol or with the sizes of exchangeable body cholesterol pools as determined by the three-pool model of cholesterol turnover. The mean plasma cholesterol level decreased 19.4% (from 294 to 237 mg/dl), and low-density lipoprotein cholesterol decreased 23.8 % (from 210 to 159 mg/dl) with lovastatin therapy. Thus, HMG-CoA reductase inhibition by lovastatin at the therapeutic dose used here did not change the steady-state rate of whole-body cholesterol synthesis. Some of the study explained that lovastatin enhanced the healing rate and increased biomechanical properties of the bone at the fracture site. Lovastatin therapies have been shown to reduce cardiovascular events, including myocardial infarction, stroke and death, significantly, by altering vascular atherosclerosis development in patients with or without coronary artery disease symptoms89. Through the analysis of the inhibitory effect on HMG-CoA reductase, it is possible to highlight the influence of the obtained structures on biological activity. The stereochemistry of the side chain ester moiety is not important for inhibitory binding to HMG-CoA reductase, as the spatial requirements of the acyl moiety are compatible with compact, branched-chain aliphatic acyl groups, and additional branching at the α carbon of the acyl moiety increases potency.


Microbial production and biomedical applications of lovastatin.

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

Structure of lovastatin All statins possess a common structure, a hexahydro-naphthalene system and a ß-hydroxylactone; their differences are due to side chains (R1) and methyl groups (R2) around the ring.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 0002: Structure of lovastatin All statins possess a common structure, a hexahydro-naphthalene system and a ß-hydroxylactone; their differences are due to side chains (R1) and methyl groups (R2) around the ring.
Mentions: Lovastatin (or mevinolin, monacolin K, and Mevacor, Merck) contains a methylbutyric side chain (R1) and a 6-α methyl group (R2) as shown in fig. 2. The foremost query addressed was whether a reduction in plasma cholesterol level with lovastatin would be associated with a reduction in the whole body production rate of cholesterol or with the sizes of exchangeable body cholesterol pools as determined by the three-pool model of cholesterol turnover. The mean plasma cholesterol level decreased 19.4% (from 294 to 237 mg/dl), and low-density lipoprotein cholesterol decreased 23.8 % (from 210 to 159 mg/dl) with lovastatin therapy. Thus, HMG-CoA reductase inhibition by lovastatin at the therapeutic dose used here did not change the steady-state rate of whole-body cholesterol synthesis. Some of the study explained that lovastatin enhanced the healing rate and increased biomechanical properties of the bone at the fracture site. Lovastatin therapies have been shown to reduce cardiovascular events, including myocardial infarction, stroke and death, significantly, by altering vascular atherosclerosis development in patients with or without coronary artery disease symptoms89. Through the analysis of the inhibitory effect on HMG-CoA reductase, it is possible to highlight the influence of the obtained structures on biological activity. The stereochemistry of the side chain ester moiety is not important for inhibitory binding to HMG-CoA reductase, as the spatial requirements of the acyl moiety are compatible with compact, branched-chain aliphatic acyl groups, and additional branching at the α carbon of the acyl moiety increases potency.

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