Benzylpenicillin manufacture

The manufacture of benzylpenicillin (penieillin G, originally just penicillin ) is chosen as a model for the antibiotic production process. It is the most renowned of antibioties and is the first to have been manufactured in bulk. It is still universally prescribed and is also in demand as input material for semisynthetic antibiotics (Chapter 5). Developments associated with the penicillin fermentation process have been a significant factor in the development of modem bioteehnology. It was a further 30 years, i.e. not until the 1970s, before there were signifieant new advances in industrial fermentations. 

Benzylpenicillin is produced as various salts according to its intended use, whether as an input to semisynthetic /3-lactam antibiotics manufacture or for clinical use in its own right. 

Penicillin (or benzylpenicillin) (32a) (R = CH2Ph) was first dicovered by Sir Alexander Fleming in 1929, who isolated the antibiotic from the fungal strain Penicillium notatum (see Introduction, p. 4). Penicillin is valuable to combat bacterial infections in man and animals. It was first manufactured commercially in 1945 and the first semisynthetic penicillins were introduced in 1954. The penicillins (32) have a common structural feature, namely a p-lactam ring fused to the... 

Like benzylpenicillin, penicillin V is still used in its own right, but can also be used as a starting material for the manufacture of semisynthetic penicillins which cannot be made by direct fermentation. 

Manufacturing processes for cephalosporin C and benzylpenicillin are broadly similar. In common with many other antibiotic fermentations, no specific precursor feed is necessary for cephalosporin C. There is sufficient acetyl group substrate available from the organism s metabolic pool for the terminal acetyltransferase reaction. 

The protein contaminants in benzylpenicillin derive from the fermentation manufacturing processes used in production of the antibiotic. During the course of fermentation, proteins of the medium become penicilloylated and may be extracted in minute amounts into the final preparations. The semisynthetic penicillins are prepared from 6-APA, which in turn is obtained through either enzymatic or chemical removal of the side chain in benzylpenicillin (Carrington 1971). Penicil-... 

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