SEMINAR-1
COURSE TITLE:PHARMACEUTICAL PROCESS
CHEMISTRY
COURSE CODE: PCS 512
M.PHARM, 2nd Semester
Date :04/09/2024
Topic :Fermentation of Lovastatin
Presented by:
Sarangi .H
M.PHARM, 2nd Sem
Register number : 23PHPY057004
Department of Pharmaceutical Chemistry
CONTENTS
Introduction
Submerged fermentation
Solid state fermentation
Purification of lovastatin
Analysis of lovastatin
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Introduction
Hyperlipidemia -elevated level of lipids — like cholesterol and
triglycerides in the blood
It leads to atherosclerosis (hardening of the arteries) and other
serious conditions like heart attack, stroke, and peripheral artery
disease
Statins are the medications that are used to control hyperlipidemia
Merck in 1979 reported Lovastatin from Aspergillus terreus ,FDA
approved in 1987
Natural-Lovastatin,Compactin
Semisynthetic-Simvastatin,Atorvastatin
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Lovastatin
Out of total body cholesterol, one-third comes from diet and nearly
two-third is synthesized in the body
Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme-A
(HMG-CoA) reductase, the rate-limiting enzyme of cholesterol
biosynthesis and lower plasma cholesterol in human and animals
Lovastatins are the natural statins produced as secondary
metabolites by various fungal organisms such as Aspergillus
spp,Penicillium spp,Monascus spp,Trichoderma spp etc
However commercial production of lovastatin employs a soil fungus
Aspergillus terreus
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Lovastatin
lovastatin (mevinolin) was the first hypocholesterolemic drug to be
approved by FDA
In the recent years, lovastatin has also been reported as a potential
therapeutic agent for the treatment of various types of tumors
because it suppresses tumor growth in vivo by inhibiting the
synthesis of non-sterol isoprenoid compounds
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Mode of action
DPP- Diketo pyrrolopyrrole , Apppl- Apoliprotein E and Proliferation inducing ligand 6
Fermentation
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Fermentation of lovastatin
Submerged fermentation (SmF) using Aspergillus terreus was used
earlier for the production of lovastatin
It was replaced by Solid state fermentation(SSF)
Use of economical substrates like agricultural residues
Fewer processing stages
Fewer downstreaming stages
Less power and effluent
Higher product yield
Better stability
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Fermentation of lovastatin
Previously, solid state fermentation was used mainly for the
production of industrial enzymes
But nowadays, it is also being exploited for the production of
secondary metabolites
Cheaply available agrowastes like rice straw, black gram
husk ,molasses ,apple waste, oil cakes ,bran etc are used as potential
substrates for the production of lovastatin
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Submerged fermentation of lovastatin
Six different nutrient media were tested for lovastatin production
To 100 ml of production medium,10 µl of spore suspension (108
spores/ml) of A.terreus was added and incubated at 30⁰C for 8 days
at 120 rpm
The different composition of lovastatin production medium are as
shown below
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Submerged fermentation of lovastatin
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Submerged fermentation of lovastatin
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Solid state fermentation of lovastatin
Various agro based materials can be used as substrate for SSF
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Solid state fermentation of lovastatin
Commercial production of lovastatin uses wheat bran as substrate
It is inoculated with spore suspension of A.terreus (107 ml of spores)
Incubated at 280C for 7 days (aeration and agitation maintained)
Inoculated substrate was dried at 400C for 24 hours
It is then crushed to powder
150 ml of ethyl acetate was added and shake at 180 rpm for 2 hours
(Harvesting and extraction)
It is then filtered with Whatman 1 filter paper
Filtrate is dried using rotary vacuum evaporator (Concentration and
crystallization)
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Purification of lovastatin
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Analysis of lovastatin by TLC
The extracted organic phase was heated and concentrated and
applied to a heat activated 20*20 cm silica gel TLC plates
Dichloromethane : Ethyl acetate (70:30) is used as the solvent
system
The plate was later observed under iodine chamber or UV light (254
nm)
Rf values obtained can be compared with standard lovastatin (0.3-
0.5)
(Sigma – Mevinolin M2147)
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Analysis of lovastatin by HPLC
A Shimadzu Liquid Chromatography model LC-10 with C-18 column
(250mm*4.6mm ) and diode array detector was used
Acetonitrile and water acidified with 0.1% phosphoric acid (60:40
v/v) was used as mobile phase
Eluent flow rate was maintained at 1.5 ml per minute and detection
was carried out at 238 nm with injection volume of 20 µl
Mevinolin (M2147) was used as standard
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Analysis of lovastatin by HPLC
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REFERENCES
1. MF.ahromi,Juan Boo Liang et.al. Lovastatin Production by
Aspergillus terreus Using Agro-Biomass as Substrate in Solid State
Fermentation.Journal of biomedicine and biotechnology,2012.
doi: 10.1155/2012/196264
2. https://www.slideshare.net/slideshow/fermentation-
230209775/230209775#50
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