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Fermentation:

Fermentation may be defined from different perspective such as-

In Biochemistry it may defined as a process that is important in anaerobic conditions when there is no

oxidative phosphorylation to maintain the production of ATP (Adenosine triphosphate) by glycolysis.

During fermentation pyruvate is metabolised to various different compounds. Homolactic fermentation

is the production of lactic acid from pyruvate; alcoholic fermentation is the conversion of pyruvate into

ethanol and carbon dioxide; and heterolactic fermentation is the production of lactic acid as well as

other acids and alcohols.

In case of Food Fermentation typically refers to the conversion of sugar to alcohol using yeast under

anaerobic conditions. A more general definition of fermentation is the chemical conversion of

carbohydrates into alcohols or acids.

In case of Biotechnology fermentation means any process by which microorganisms are grown in large

quantities to produce any type of useful materials.

Pharmaceuticals and the biotechnology industry:

There are 5 major groups of commercially important fermentation:

1. Microbial cells or biomass as the product, e.g. bakers yeast, lactobacillus, etc.1. Microbial enzymes: catalase, amylase, protease, pectinase, glucose isomerase, cellulase, hemicellulase,

lipase, lactase, streptokinase, etc.

2. Microbial metabolites :1. Primary metabolites ethanol, citric acid, glutamic acid, lysine, vitamins, polysaccharides etc.2. Secondary metabolites: all antibiotic fermentation3. Recombinant products: insulin, HBV, interferon, GCSF, streptokinase4. Biotransformation: phenyl acetyl carbinol, steroid biotransformation, etc.

Requirements for Fermentation:

For carrying out the fermentation process various goods are required which include-

1. Fermenters:

The heart of fermentation process is fermenter. A working definitions of a fermenter is a container in

which, is maintained an environment favorable to the operation of a desired biological process. The

common features of typical fermenters are as follows-

They should be strong enough to withstand the pressure exerted by large volume of the medium. The material used for the construction of fermenter should not be corroted by the fermentation product

and it should not yield toxic ions to the medium.

The fermenter should have provision for the control or prevention of the growth of contaminatingmicroorganisms. This is a must because the industrial fermentation requires pure cultures.

If aerobic organisms are used in the process, there should be provision for rapid incorporation of sterileair into the medium so that the oxygen is immediately dissolved in the medium and available to the

microorganisms.

The carbon dioxide produced by the microorganisms should be removed from the medium andprovision should be made for this.

Certain kind of stirring is necessary to mix the organisms with medium and to make nutrients andoxygen available to individual microbe.

A system should be available for detection of PH of the culture medium and also for its adjustment.


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2. Microorganisms:

Many species of microorganisms are used for carrying out the process of fermentation to produce useful

products. They include-

Bacteria- Acetobacter lacti, Bacillus subtilis, Bacillus polymyxa, Acetobacter woodi etc.

Algae- Spirulina maxima, Chlorella sorokiniana, Sorokiniana platensis etc.

Fungi- Aspergillus oryzae, Aspergillus niger, Candida utilis etc.

Actinomycetes- Nocardia mediterranei, Streptomyces griseus etc.

3. Fermentation Medium:

Growth media are required for industrial fermentation, since any microbe requires water, oxygen, an

energy source, a carbon source, a nitrogen source and micronutrients for growth.

Carbon & energy source + nitrogen source + O2 + other requirements Biomass + Product +

byproducts + CO2 + H2O + heat.

Nutrient

Raw MaterialsCarbon Source

Glucose

corn sugar, starch, cellulose

Sucrose

sugarcane, sugar beet molasses

Lactose

milk whey

Fats

vegetable oils

Hydrocarbons

petroleum fractions

Nitrogen Source

Protein

soybean meal, corn steep liquor, distillers' soluble

Ammonia

pure ammonia or ammonium salts

urea

Nitrate

nitrate salts

Phosphorus source

phosphate salts

Trace elements:

Fe, Zn, Cu, Mn, Mo, Co

Antifoaming agents :

Esters, fatty acids, silicones, sulphonates, polypropylene

Buffers:

Calcium carbonate, phosphates

Growth factors:


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Some microorganisms cannot synthesize the required cell components themselves and need to be

supplemented, e.g. with thiamine, biotin, calcium pentothenate

Precursors:

Directly incorporated into the desired product: Phenyl ethylamine into Benzyl penicillin, Phenyl acetic

acid into Penicillin G

Inhibitors:

To get the specific products: e.g. sodium barbital for rifamycin

Inducers:

The majority of the enzymes used in industrial fermentation are inducible and are synthesized in

response of inducers: e.g. starch for amylases, maltose for pollulanase, pectin for pectinase,olive oil and

tween are also used at times.

Chelators:

Chelators are the chemicals used to avoid the precipitation of metal ions. Chelators like EDTA, citric acid,

polyphosphates are used in low concentrations.

Process of Fermentation:

Process of fermentation varies from product to product. Some of these processes for particular material

are given below-

In case of Streptomycin production fermentation process is carried by the following phase-

Phase-1: In the first 24 hours, growth of the organism starts in the form of mycelium. Streptomyces

grisus releases NH3 from soyabean. Glucose is utilized slowly in this period. Production of mycelium is

very slight in this phase. The PH is around 6.7 or 6.8-7.5.

Phase-ii: Streptomycin production is rapid after 24 hours and continues up to 6 or 7 days. Fairly constant

mycelium growth occurs during this period. Glucose is used completely from the medium. The PH of the

medium is about 7.6 to 8.

Phase-iii: After complete utilization of glucose, the growth ceases. Autolysis takes place (the cells are

lysed) and ammonia is released. Hence the PH rises. The mycelium produced is taken for the recovery of

antibiotic.

In case of Tetracycline production fermentation process is carried by the following-

The commercial method of production of Tetracycline is to subject chlortetracycline to simultaneous

dechlorination and hydrozination. Chlortetracycline is dissolved in a solvent like methyl cellulose

containing palladium, charcoal and tri ethyl amine as catalyst. Hydrogen is passed at room temperature.

Hydrogenation is completed in about 20 minutes. Tri ethyl amine is neutralized with HCl and it is

removed by pouring the reaction mixture into water where tetracycline base is crystallized.

Tetracycline can also be produced by fermentation process using selected strains of Streptomyces

aureofaciens. In this process, inhibitors of chloride utilization such as bromide and organic thiol

compound are added to the chlortetracycline producing culture. In another method, chloride free

medium is used. The fermentation conditions are similar to chlortetracycline.

In case of L-lysine production the process is

The medium consist of glycerol, corn steep liquor and [NH4]2HPO4. E.coli is grown on the medium

under controlled condition PH, temperature and aeration to produce optimum quantity of DAP. The


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incubation is done for about three days. After three days DAP decarboxylase is added to convert DAP to

L-lysine which is later extracted.

In case of cyanocobalamine production-

The final medium is inoculated with 5 % of inoculums and incubated for stipulated time period to

produce the mycelium. Animal or plant extract containing traces of cyanocobalamine is added to culture

for best production. Sporulation occurs in 4 to 6 days at 280C. These spores can be stored by freeze

drying in sealed vial.

In case of Lactic acid production by fermentation-

Lactic acid fermentation is carried out in tanks made up of wood or lined with stainless steel to

withstand the corrosive nature of lactic acid. The fermentation is carried out at a PH of 5.5 to 6.5 and

temperature of 45-500C for 6 days. The medium is agitated continuously to keep CaCO 3 in suspension

to neutralize the lactic acid produced. After 6 days, the broth contains 80-90 percent of lactic acid. The

temperature is high to avoid the contamination of butyric acid producing bacteria.

Biologicals obtained from fermentation:

From fermentation technology we get various types of biologicals or chemical goods. Some of these areshown below in a tabular form-

Products

Microorganisms

Industrial Chemicals

Ethanol ( from glucose)

Saccharomyces cerevisiae

Ethanol ( from lactose)

Kluyveromyces fragilis

Citric AcidAspergillus niger

Gluconic Acid

Aspergillus niger

Acetic Acid

Acetobacter spp.

Lactic Acid

Lactobacillus delbrueckii

Amino Acids

L-lysine

Corynebacterium glutamicium

MSG


Glutamic Acid


Vitamins

Riboflavin

Ashbya gossypi

Vitamin B12

Pseudomonas denitrificans


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Ascorbic Acid(L-sorbose)

Gluconobecter oxidans

Enzymes

Amylase

Aspergillus oryzae

Cellulase

Trichoderma reesii

Invertase

Saccharomyces cerevisiae

Lipase

Saccharomyces lipolytica

Protease

Bacillus

Polysaccharides

Dextran

Leuconostoc mesenteroids

Xanthan Gum

Xanthomones compestrisPharmaceuticals

Penicillin

Penicillin chrysogenum

Cephalosporin

Cephalosporium acemonium

Amphotericin B

Streptomyces nodosus

Kanamycin

Streptomyces kanamyceticus

Neomycin

Streptomyces fradiaeStreptomycin

Streptomyces graseus

Gramicidin S

Bacillus brevis

Polymyxin

Bacillus polymxa

Chloramphenicol

Streptomyces venezuelae

Erythromycin

Streptomyces erythreus

Steriodal Transformations

Rizopus nigricans

Steriodal Transformations

Arthrobacter simplex

Viva A (adenine arabinoside)

Streptomyces antibiotioticus


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Comments:

Fermentation; which is an ancient process has been using different fields over the time. Using of

fermentation in Biotechnology enlarge the scope of it. Various types of materials are synthesized in

biotechnology by using fermentation which is used in different useful tasks. In drug development, the

application of fermentation is also undeniable. By using fermentation various life savings drugs are

synthesized (i.e. antibiotic, enzymes, amino acids etc.). So, from the above discussion we can easily say

that fermentation technology is very much important in drug development.

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