Microbial Production of Antibiotics by fermentation & synthesis
Production of antibiotics is very critical to meet the market demands of health care system. Antibiotics are secretions from a certain strain of bacteria to restrict the growth of other bacteria around them. So by natural process, their formation is quite small to meet large demands of humans patients worldwide.
In the initial phases of discovery, the production was so meager that some patients who were on the way of a fine recovery from dreadful infections by their use died due to lack of sufficient supply of antibiotics.
Hence there were combined efforts of US & other governments, pharma industries and scientists from to design methods for surplus production of antibiotics. Hence they came up with techniques like fermentation by use of recombinant DNA technology combined.
Latter on to improve their efficiency these natural antibiotics were modified in-terms of their chemistry. Thus there was a development of semi-synthetic derivatives.
Further antibiotics are also obtained by pure synthesis using chemicals for example, ciprofloxacin & norfloxacin group.
So production of antibiotics can be done by 3 methods.
1. Natural microbial production using fermentation technology.
2. Semi-synthetic production. (Post-production modification of natural antibiotics).
3. Synthetic production of antibiotics.
Microbial production of antibiotics
Antibiotics produced by microbes are very minute in quantity. Hence to produce them in large quantities techniques like rDNA technology, fermentation are used.
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 which has small 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 short time.
The fermentation technology used to grow these cloned microbes adopt techniques like synchronous growth and continuous growth. These two techniques contribute to profuse and also continuous production of antibiotics in the culture broth.
Semi-synthetic production: The antibiotics produced by above methods are effective but still have some limitations. The limitations include 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 addition of functional groups to ampicillin, amoxicillin.
While some antibiotics are produced from their origin compound by 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 which are produced by the above methods include families of tetracycline, streptomycin, erythromycin, etc.
Synthetic antibiotics production: Synthetic antibiotics have been used to a large extent as they are cheaper in comparison to natural ones. Further, they have fewer side effects and can be synthesized in an easy procedure.