Benzylpenicillin penicillin fermenter

PhCHa benzylpenicillin = penicillin G (usual fermentation product)... 

Naturally occurring. For example, those produced by fermentation of moulds such as Penicillium notatum and P. chrysogenum. The most important examples are benzylpenicillin (penicillin G) and phenoxymethylpenicillin (penicillin V). 

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. 

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. 

It certainly does. For one thing the earliest penicillins like benzylpenicillin (penicillin G) are decomposed by acid. The contents of our stomachs are strongly acidic, so that these penicillins could not be taken orally but had to be iryected. It was found that when phenoxyacetic acid was added to the fermentation broth, the resulting phenoxymethylpenicillin, commonly known as penicillin V, was fairly acid-stable and could be taken by mouth. Subsequently many more oral penicillins like this have been developed. 

The acylation of 6-APA (Scheme 59) has been a very versatile way in which to generate new penicillin derivatives which differ from fermentation-produced penicillins in the 6-side chain. As will be discussed in Section 5.11.5.1, this approach has led to significant improvements in the therapeutic properties of penicillins, and, in fact, of the penicillins in medical use today, only benzylpenicillin and phenoxymethylpenicillin are produced directly by fermentation. 

Following the realization that the presence of phenylacetic acid in the fermentation led to a simplification of the mixture of penicillins produced by the fungus due to preferential uptake of this acid and its incorporation into benzylpenicillin (4), a wide variety of other acids were added to the growing culture. Inclusion of the appropriate acids in the culture medium thus afforded, respectively, phenoxymethylpenicillin (5, penicillin V), phenethicillin propicillin (7), and phehbencillin... 

In a multiphase membrane reactor, the conversion of benzylpenicillin to 6-aminopenidllinic acid is performed. The type of microstructured reactor used is a fermentation reactor which contains the enzyme penicillin acylase immobilized on the wall of a hollow-fiber tube. The hollow-fiber tube extracts 6-aminopenicillinic acid at the same time selectively. Benzylpenicillin is converted at the outer wall of the hollow fiber into the desired product, which passes into the sweep stream inside the fiber where it can be purified, e.g. by ion exchange. The non-converted benzylpenicillin is recycled back through the reactor [84],... 

Several natural penicillins can be produced, depending on the chemical composition of the fermentation medium used to culture penicillium. Penicillin G (benzylpenicillin) has the greatest antimicrobial activity of these natural penicillins and is the only natural penicillin used clinically. However, penicillin G is not stable it is extremely acid-labile. Only about one-third of an oral dose is absorbed under the most ideal conditions. Therefore, it is generally not given orally but is administered by intramuscular injection. Several newer derivatives of penicillin G have been developed that do have good to excellent oral absorption (e.g., cloxacillin, ampicillin, and amoxicillin). 

It is possible to convert penicillin V or benzylpenicillin to a cephalosporin by chemical ring expansion. The first-generation cephalosporin cephalexin, for example, can be made in this way. Most cephalosporins used in clinical practice, however, are semi-synthetics produced from the fermentation product cephalosporin C. 

Both benzylpenicillin and phenoxymethy1 penicillin are produced commercially by fermentation. However, from the beginning of the vast British-American cooperative program during World... 

During the same period, Sheehan was working toward a total synthesis of penicillins. In 1958, he announced the synthesis of 6-amino-penicillanic acid (6-APA) and its utility for the preparation of new penicillins by acylation (67, 68). (Almost 10 years earlier, this substance had been postulated to be an intermediate in the biosynthesis of penicillins (69, 70). Prior Japanese literature also contained clear suggestions that it had been formed by enzymatic hydrolysis of benzylpenicillin (71) and in fermentations carried out in the absence of side chain precursors... 

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-... 

The penicillins and cephalosporins, collectively known as beta-lactam antibiotics, are among the most widely used and valuable antibiotics currently available. Ben-zylpenicilhn (penicillin G) and phenoxymethylpenicillin (penicillin V) are derived from Penicillium molds by fermentation, while half-synthetic penicillins are derived by chemical modification of the penicillin nucleus, 6-aminopenicillanic acid (6-APA), itself obtained either by splitting the side chain from benzylpenicillin through an enzymatic process or via a chemical deacylation reaction. 

Aminopenicillanic acid (6 APS) is an important precursor for the organic synthesis of new P. The compound itself has no antibiotic activity it is isolated as a fermentation product from cultures of Pen-cillium chrysogenum, or prepared by the enzymatic hydrolysis of benzylpenicillin. Thousands of new P. have been prepared by the acylation of 6 APS, but only a few of these are therapeutically useful, e.g Penicillin V is relatively stable to acid and is not hydrolysed in the stomach, so that it may be administered in tablet form Ampicillin (the aminophenyl-acetyl derivative of 6 APS), has a wider spectrum of activity than most other R, including activity against various Gram-negative bacteria (Typhus, E. coli, etc.). 

An interesting use of mixed radioisotope and stable isotope labelling was demonstrated when the formation of benzylpenicillin by Penicillium chryso-genum in the presence of L- and D-[3- C, N, S]cystine was studied. The penicillin isolated contained the three labels in their proportions in the precursor when L-cystine had been added to the fermentation medium. It was concluded that cystine was a direct precursor of penicillin, probably after reduction to cysteine [215]. 

Yes. While in the United States, Heatley found that the addition of different chemicals to the fermenting liquor created different penicillins. Most significantly, adding phenylacetic acid gave rise to penicillin G, later called benzylpenicillin. 

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