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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

Biosynthesis of lovastatin The lovastatin biosynthetic pathway starts from acetate units linked to each other in head- to-tail fashion to form two polyketide chains. Monacolin L is first produced from acetate and methionine and then hydroxylated to monacolin J by a monooxygenase. Monacolin J is further converted to monacolin X by an esterification reaction, followed by transformation into the end-product lovastatin.
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Figure 0003: Biosynthesis of lovastatin The lovastatin biosynthetic pathway starts from acetate units linked to each other in head- to-tail fashion to form two polyketide chains. Monacolin L is first produced from acetate and methionine and then hydroxylated to monacolin J by a monooxygenase. Monacolin J is further converted to monacolin X by an esterification reaction, followed by transformation into the end-product lovastatin.

Mentions: An intramolecular Diels-Alder endo closure of the hexaketide, to form a bicyclic system, with the same ring stereochemistry as dihydromonacolin L, catalyzed by LNKS purified from A. nidulans was recently demonstrated. Finally in a strain of A. terreus, in which the lovC gene has been disrupted, the post-PKS (post-polyketide synthase) steps involved in the biosynthesis of lovastatin were investigated. The results demonstrated that the role of the lovC protein is to ensure correct assembly of the nonaketide chain in lovastatin by the lovB protein. In contrast, the construction of the methylbutyrate side chain by the LDKS (lovF protein) does not require lovC protein. The study also demonstrated that the lovC protein has no detectable function in post-PKS processing of dihydromonacolin L. The recent advances in gene cloning have allowed the identification of most of the enzymes involved in lovastatin biosynthesis and have confirmed the biosynthetic pathways hypothesized in earlier investigations2122. The detailed process of biosynthesis of lovastatin is shown in fig. 3.


Microbial production and biomedical applications of lovastatin.

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

Biosynthesis of lovastatin The lovastatin biosynthetic pathway starts from acetate units linked to each other in head- to-tail fashion to form two polyketide chains. Monacolin L is first produced from acetate and methionine and then hydroxylated to monacolin J by a monooxygenase. Monacolin J is further converted to monacolin X by an esterification reaction, followed by transformation into the end-product lovastatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 0003: Biosynthesis of lovastatin The lovastatin biosynthetic pathway starts from acetate units linked to each other in head- to-tail fashion to form two polyketide chains. Monacolin L is first produced from acetate and methionine and then hydroxylated to monacolin J by a monooxygenase. Monacolin J is further converted to monacolin X by an esterification reaction, followed by transformation into the end-product lovastatin.
Mentions: An intramolecular Diels-Alder endo closure of the hexaketide, to form a bicyclic system, with the same ring stereochemistry as dihydromonacolin L, catalyzed by LNKS purified from A. nidulans was recently demonstrated. Finally in a strain of A. terreus, in which the lovC gene has been disrupted, the post-PKS (post-polyketide synthase) steps involved in the biosynthesis of lovastatin were investigated. The results demonstrated that the role of the lovC protein is to ensure correct assembly of the nonaketide chain in lovastatin by the lovB protein. In contrast, the construction of the methylbutyrate side chain by the LDKS (lovF protein) does not require lovC protein. The study also demonstrated that the lovC protein has no detectable function in post-PKS processing of dihydromonacolin L. The recent advances in gene cloning have allowed the identification of most of the enzymes involved in lovastatin biosynthesis and have confirmed the biosynthetic pathways hypothesized in earlier investigations2122. The detailed process of biosynthesis of lovastatin is shown in fig. 3.

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