Production of Penicillin

Introduction image

The production of penicillin is used commercially to treat various infections caused by the gram-positive aerobic bacteria. Penicillin is a narrow-spectrum antibiotic that is found effective against many gram-positive bacteria, especially Streptococcus and Staphylococcus  species. There are approximately 100 penicillins that have been synthesized so far.

For the production of penicillin, different strains of Penicillium strain are being used.  Now P. chrysogenum is used for the high yield of penicillin (50 g/dm3).

Content: Production of Penicillin

  1. Definition
  2. Penicillin
  3. Production Process
  4. Uses
  5. Conclusion

Definition

The production of penicillin is an industrial process that commercially produces penicillin by using the fungus (P. chrysogenum) and the feedstock containing desired N-source, C-source, and minerals etc. It uses the fed-batch culture method. The penicillin produced as a secondary metabolite by the microorganism, which is then recovered from the feedstock solution.

Its production is medically important to cure infections caused by the gram-positive Staphylococci and Streptococci species. The penicillin inhibits the bacterial activity by inactivating the penicillin-binding proteins that are present inside the cell wall, and finally destroys the cell wall synthesis of such bacteria.

What is Penicillin?

It is one of the most important antibiotics derived from the fungal mould called Penicillium notatum or Penicillium chrysogenum. It acts as a cell wall destroyer of bacteria. The word “Penicillin” was originated from the Latin word “Penicillium” which means “a painter’s brush” as the fronds of fungus was looked like a painter’s brush. Nowadays, many different derivatives of penicillin are prepared, which kills more bacteria than penicillin. It is useful in killing different types of bacteria like Streptococcus pneumoniae, Listeria, etc.

Structure of penicillin

The structure of penicillin differs from its side chain linked to the amino group. In this article, we will focus on the structure of penicillin G, which consists of side acyl chain, β lactam ring and thiazolidine ring. The β lactam ring is responsible for the antimicrobial activity that is useful to destroy the cell wall synthesis of gram-positive bacteria, especially Staphylococcus and Streptococcus species.

Properties of Penicillin G

Penicillin G is a secondary metabolite formed during the stationary phase. Some of its physical and chemical properties are mentioned below in the table.

Chemical Properties

  • Molecular Formula: C16H18N2O4S
  • Molecular weight: 334.4 g/mol
  • Formal charge: Zero
  • Density: 1.41
  • Solubility: It is insoluble in petroleum ether, sparingly soluble in water and readily soluble in organic solvents like methanol, ethanol, benzene etc.

Physical Properties

  • Physical state: Solid
  • Colour: Amorphous white powder
  • Odour: Odourless
  • Melting point: 214-217 degrees Celsius

History

A scientist named Alexander Fleming (Professor of Bacteriology) introduced penicillin in the year 1928. Once he was cleaning his messy lab and observed that Petri dishes which was contained with Staphylococcus bacteria was contaminated with mould.

That mould was named as Penicillium notatum, and he found that Penicillium notatum was preventing the growth of bacteria. Fleming called an active agent of Penicillium notatum as “penicillin” and found that it kills many different types of bacteria.

Production Process

The commercial production of penicillin is shown below. Most of the antibiotics follow the same method for its commercial production in the industry. Majorly difference lies in the following three things – Microorganisms used, the composition of media and procedure used in extraction. Industrial production of penicillin is carried out in the steps mentioned below:

production process of penicillin

Inoculum Preparation

The culture of P. chrysogenum strain is preserved as a lyophilized spore. Firstly, P. chrysogenum is cultured into a flask for seven days at a temperature of 24 degree Celsius with a wheat bran nutrient solution. After this phase, we can get a high yield strain of P. chrysogenum.

Transfer of Inoculum

Now to support mycelial growth, the prepared culture is shifted to inoculum or seed tank. Here, the culture is kept under proper aeration and agitation, and left to grow for 1-2 days. This stage generally refers to as “Growth phase”.

Fermentation

Now the inoculum is added into a fermentor filled with production medium or feedstock solution that consists:

  • 10% total C6H12O6 (glucose)/molasses
  • 4-5% corn-steep liquor solids
  • 0.5-0.8% C8H8O2 (phenylacetic acid)
  • 0.5% vegetable oil.

Then pH is set to 6.0 and temperature ranges between 25-26 degree Celsius. The fermentation process is completed under aerobic conditions, and for nutrient supply, regular feeding (fed-batch culture) is maintained. The fermentation process requires one week for the penicillin production.

Initially, available carbohydrates are used due to the growth of mycelial, by which reduction in carbohydrate level occurs in the medium. Because of this reduction in carbohydrate level, penicillin production begins from 2nd day of fermentation. Then by the end of 7th day, pH of medium rises to 8.0 and at this stage production of penicillin stops.

Filtration

The production of Penicillin G increases due to the presence of the precursor. Here, Phenylacetic acid acts as a precursor for benzene ringside chain of Penicillin G. Now, the filtration process is used to separate the fungal biomass and used as a feed supplement for animals at the end of the fermentation period.

Extraction

Penicillin G is extracted from broth using an organic solvent. Finally, after purification, penicillin G is produced as a potassium salt and then transformed into 6-aminopenicillins acid (6-APA). And then finally side chain of 6-APA can be modified in various forms to get different derivatives of penicillin, which can be utilized in medicine.

Uses

  • Different kinds of infections like pneumonia, respiratory tract and throat infections can be treated by using Penicillin V potassium.
  • Penicillin V potassium prevents rheumatic fever.
  • It sometimes also used in the treatment of anthrax infections of the skin.
  • It also used with other medicine to treat diphtheria.
  • Penicillin V potassium also treats heart valve infections.

Conclusion

Therefore, the production of penicillin is a vital process in the field of medical biology, as it functions as an antibiotic that inhibits the bacterial activity or the infections caused by the various gram-positive microorganisms.

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