Microbial Processes for the Production of Penicillin and Alkaloids

The processes which are required to produce penicillin and alkaloids are generally microbial processes as these antibiotics are microbial. The world’s first antibiotic was discovered in the year 1896 by the French physicist Ernest Duchesne, who observed that some of the molds hold the property to kill bacteria. After 32 years Alexander Fleming in 1928 discovered the antibiotic properties of penicillin, a substance derived from those molds, he observed that the fungus, Penicillium notatum Is preventing the biological growth or maturity in bacteria, Staphylococcus. There are various uses of penicillin in the pharmacy sector as an alkaloid that means a medicinal drug. There are various uses of alkaloids that are helpful to human society as far as health is concerned. This makes a person excited to know exactly what penicillin means. 

What is penicillin?

Everyone in their lives must have heard about the term penicillin and rather than trying to know more about it we generally tend to move forward with our daily chores. It is the world’s first antibiotic and has vital importance in medicinal research evolution. It was first discovered in 1928 by  Alexander Fleming accidentally. As he observed the fungus, Penicillium notatum hindered and stopped the basic growth of bacteria, Staphylococcus spp. And by this the world’s first antibiotic got recognition.

Types of Penicillin

Penicillin has two types, Penicillin F and Penicillin G (Benzylpenicillin, a narrow-spectrum antibiotic). Penicillin F (Fentanyl Penicillin). These two classes of antibiotics are widely used in treating both types of (Gram-positive and Gram-negative )infections. When we extract Penicillin (Natural) we obtain it as potassium or sodium salts. 

Some examples of Penicillin are Oxacillin, Piperacillin Ampicillin, Cloxacillin, etc.

Biological synthesis of Penicillin

Penicillin biosynthesis could be described into following three main steps;

1. Catalytic step

The step involves an enzyme named ACV synthetase that condenses the lateral chain of valine, cysteine, and alpha aminoadipate into tripeptide ACV.

2. Oxidative step

In this, tripeptide ACV forms a bicyclic ring by oxidative ring closure. Isopenicillin N synthase is involved leading to isopenicillin N which may be a bioactive intermediate within the pathway.

3. Exchange of varied chains

This final step involves the exchange of L-aminoadipate. The conversion of Penicillin N from isopenicillin N is aided by the involvement of a 2-enzyme system(Acyl-CoA synthetase and Acyl-CoA racemase).
And by this, we get Penicillin N.

• Note- The biological synthesis of penicillin is tough at commercial scale because of high time consumption and lower yields, to grow yield the following process is used at commercial levels.

Penicillin Production Process

For the commercial yield of Penicillin, P.chrysogenum is used. 

Penicillin is produced by the process of fermentation.

The culture of P.chrysogenum  is agitated under a favorable (aerobic)condition in a fermenter to produce Penicillin. The involved method is fed-batch.

The Penicillin G production process (fermentation) involves some simple steps which are:

1. 100ml medium with spores of P.chrysogenum strains is inoculated in Erlenmeyer flask and is incubated at BOD incubator by placing them on a rotatory shaker.
2. After 4 days of incubation, the content along with two liters of medium is transferred into a flask that contains four liters and again incubates for two days.
3. Then, the content is transferred into a stainless tank containing 500 ml of the medium that provides suitable conditions for fungal growth. 
4. After three days of incubation, the content is used for inoculation and kept in a fermentor that is well equipped with optimum conditions. 
5. The content is filtered after six days of incubation which contains penicillin. 
6. Then penicillin could be extracted into butyl or amyl acetate and then placed into an aqueous solution with phosphate buffer.
7. Acidify the extract and again re-extract penicillin into butyl acetate
8. In the solvent extract potassium acetated is added to a crystallization tank to crystallize as a potassium salt.
9. Crystals were recovered and further sterilization of salt is done.

Uses / Application of Penicillin

Used in the treatment of infections(caused by both Gram+ve and Gram-ve bacteria) such as mouth, throat, gum, respiratory tract infections, urine infections and also used in treating bacterial endocarditis. 

What does Alkaloid mean?

Alkaloids(alkali-like) are the naturally occurring compounds(toxin amines), organic in nature, which contain nitrogen atom/atoms in their structures. In pure form, alkaloids are colorless crystalline solids that are odorless. Alkaloids are the secondary metabolites and are extremely important, especially for human beings. They show strong effects even in very small doses on human beings and animals. They are also present as various stimulant drugs. They show antimicrobial, antifungal, analgesics, pain relief, and various other activities.

Examples of alkaloids are

In plants, (Papaver somniferum) Opium poppy, and (Claviceps) the ergot fungus.

In animals like New world beaver(Castor canadensis), lizards, frogs( poison dart frogs (Phyllobates))

Uses of Alkaloids

They are very useful as diet supplements, diet ingredients, in medicine pharmaceuticals, and several other applications in day-to-day life.

Some Popular alkaloids are- Morphine, nicotine, quinine, strychnine, caffeine, atropine, and ephedrine.

Medicinal use-  to relieve pain by the limited use of morphine and atropine.

Conclusion

The topic of the microbial processes of production of penicillin and alkaloids has looked into what is penicillin or alkaloids means. Moreover, it has also looked into the production processes of penicillin, in great detail. The various uses of penicillin and alkaloids have been discussed under the topic. The FAQs section attempts to address the most probable queries that might arise. The FAQs section provides additional information which will aid a better understanding of the topic.