Production of fermentation

1. Presented by:
Komal jain
M. Pharm
Pharmaceutical Chemistry

2. 
• Introduction
• History of statins
• Mode of action
• Production of statins by fermentation
• Lovastatin
• Simvastatin
• Applications
CONTENT

3. 
• The statins act as competitive inhibitors, specifically inhibiting
HMG-CoA reductase, a rate limiting step cholesterol
biosynthesis. Statins block the conversion of HMG-CoA
reductase to malonic acid in the mevalonate pathway .
 Class of statins:
 Natural Statins: Lovastatin(mevacor), Compactin, Pravastatin
(pravachol), Simvastatin (Zocor).
 Synthetic Statins: Atorvastatin (Lipitor),Fluvastatin (Lescol).
Introduction

4. 
History of statins
4
4

5. 
 Lovastatin are natural statins produced as secondary metabolites
by predominantly Aspergillus and Penicillium species.
 Lovastatin produced by a fungus, Aspergillus terreus isolated
by us from tropical soil. Lovastatin was one of the first
cholesterol-lowering drugs.
 Simvastatin is obtained a selective enzymatic deacylation of
lovastatin.
 Many statins are now chemically synthesised but lovastatin is
still required to produce simvastatin
 From reducing blood cholesterol levels simvastatin causes
pleotropic effects and has potential to treat various kinds of
disorders including neurodegenerative disease .
Lovastatin

6. 
Mode of action (lovastatin)

7. Production of natural and semi-synthetic statins by fungi.
Simvastatin Pravastatin

8. Fermentation method of lovastatin
Wheat bran (40g) as substrate
Inoculated with spore suspension (107/8ml spores) of A. terreus .
Incubated at 280C for 7 days
Culturing of A.terreus by Solid State Fermentation
(SSF)
8

9. Inoculated substrate was dried at 40◦C for 24h
Crushed to powder
Ethyl acetate (150 ml) was added
Filtrate was dried using rotary vacuum
evaporator
9

10. One gram of dried crude lovastatin extract was loaded
on to pre-packed silica gel column
Elution with benzene (100%),
And combination of Benzene: Acetonitrile in the following ratio
95:5, 90:10, 85:15, 80:20
Acetonitrile (100%)
Thin Layer Chromatography (TLC)
Purification of lovastatin
10

11. 
 Statins also reduce hepatic cholesterols leading to reduced gall stone
formation and reduced platelet aggregation.
 Simvastatin has been found to reduce the incidence of
neurodegenerative disorders such as Alzheimer’s disease and
Parkinson’s disease.
 Lovastatin had proven to reduce the coronary heart diseases (CHD) in
the patients, by lowering the plasma cholesterol level.
 Lovastatin is reduce proliferation of Lung cancer ,Breast cancer,
Liver cancer and cervical cancer.
Application

12. 
 Subhan, M. et al. (2016) Exploitation of Aspergillus terreus for
the production of natural statins. J Fungi 2, 1–13.
doi:10.3390/jof2020013.
 Wolozin, B. et al. (2007) Simvastatin is associated with a
reduced incidence of dementia and Parkinson’s disease. BMC
Med. 5, 20. doi:10.1186/1741-7015-5-20.
 Latha, D. Prasanna, KPJ Hema Latha, and D. Sri Rami Reddy.
"Production of lovastatin by solid state fermentation by
Penicillium funiculosum NCIM 1174."Drug Invention
Today 3.6 (2011).
 Lee, T. J. H., W. J.; Smith, R. L. Journal of Organic Chemistry
1982, 47, (24), 4750
References