Antibiotics are essential medicines to treat bacterial infections.
They are required in large quantities and hence their production is very critical to meet the market demands of the health care system.
Antibiotics are natural products secreted by certain strains of fungus and bacteria to restrict other bacteria’s growth.
In the initial stages of discovery, their production was meager. Due to this, patients who were on the way to a fine recovery died due to a lack of sufficient supply of antibiotics for treatment.
Hence there were combined efforts by the US & other governments, including pharma industries and scientists, to design methods for the surplus production of antibiotics.
Later on, to improve their efficiency, these natural antibiotics were modified in terms of their chemistry. Thus there was a development of semi-synthetic derivatives.
Few antibiotics like ciprofloxacin & norfloxacin are obtained by pure synthesis using chemicals.
So antibiotic production can be done by 3 methods.
- Natural microbial production using fermentation technology.
- Semi-synthetic production. (Post-production modification of natural antibiotics).
- Synthetic production of antibiotics.
Microbial production of antibiotics
Antibiotics produced by microbes are very minute in quantity. Hence to have them in large quantities, techniques like rDNA technology and fermentation are used.
Fermentation is a process used to grow profuse quantities of bacteria in a controlled environment.
The bacteria, during fermentation, grow, multiply, and also secretes large quantities of antibiotics.
The growth in fermentation tank shows three stages like
- Lag phase
- Log phase
- Stationary phase or Plateau and
Antibiotics are produced during stationary phase along with other metabolites.
However, each bacterial strain has its own cell cycle. So, bacteria with a longer cycle span will take more time to produce antibiotics.
In contrast, the strains like E-coli have a cell cycle of just 15 to 20 minutes.
Due to this short cell cycle, huge amounts of antibiotics are produced in a given time.
So, such strains with low cycle span are chosen and the antibiotic production mechanism is inserted into its genome by rDNA technology. This is then subjected to fermentation.
Recombinant DNA technology:
Antibiotic formation depends on the number of microbes, their multiplication time, their inherent tendency to produce these chemicals. All these factors are not controllable as such by man.
So we use recombination technology to transfer the gene-producing antibiotic into a microbe that has a short multiplication time.
Further, these cloned microbes are grown in nutrition media (by fermentation technology), which supports their profuse growth to yield large quantities of antibiotics in a short time.
The fermentation technology used to grow these cloned microbes adopt techniques like synchronous growth and continuous growth.
These two techniques contribute to the profuse and also continuous production of antibiotics in the culture broth.
The antibiotics produced by the above methods are effective but still have some limitations. The limitations include the low duration of action, low distribution inside the body, side effects to patients, etc.
These limitations are overcome by chemical modification. For example, penicillin produced by microbes is modified by adding functional groups to ampicillin, amoxicillin.
Besides, few antibiotics are produced from their origin compound by the use of immobilized enzymes.
1. To convert Pencillin-G to ampicillin
Pencillin-G ——–IME Penicillin amidase———-> 6-amino penicillanic acid
6-amino penicillanic acid ——–IME Penicillin amidase———-> Ampicillin.
2. Production of cephalexin
7-Phenylacetamido desacetoxy cephalosporanic acid —IME cephalosporin amidase——-> Cephalexin.
The other antibiotics produced by the above methods include families of tetracycline, streptomycin, erythromycin, etc.
Synthetic antibiotics production
Synthetic antibiotics have been used on a large scale as they are cheaper than natural ones. They also have fewer side effects, and the chances of development of antibiotic resistance are low.
They are synthesized by a normal chemical reaction in an established procedure.
What phase are antibiotics produced?
In fermentation, bacteria produce antibiotics in the third phase i.e. stationary phase.
Which microorganisms are used in the production of antibiotics
Specific bacteria can produce specific antibiotics. But by recombination technology, E.coli is used to produce antibiotics.