Biocatalysis penicillin

Bruggink (1996) has given an account of how the production of cefalexin, which is the largest cephalosporin in the market, can be converted from a ten-step process based on benzaldehyde and penicillin into a six-step process where biocatalysis is involved in three steps. The wastewater stream, containing 30-40 kg of unwanted materials in the conventional process, has been substantially reduced. Similarly, Van Loon et al. (1996) have given details of fermentation processes for cleaner and cheaper compared to the process practised so far. 

Some of the industrial biocatalysts are nitrile hydralase (Nitto Chemicals), which has a productivity of 50 g acrylamide per litre per hour penicillin G amidase (Smith Kline Beechem and others), which has a productivity of 1 - 2 tonnes 6-APA per kg of the immobilized enzyme glucose isomerase (Novo Nordisk, etc.), which has a productivity of 20 tonnes of high fmctose syrup per kg of immobilized enzyme (Cheetham, 1998). Wandrey et al. (2000) have given an account of industrial biocatalysis past, present, and future. It appears that more than 100 different biotransformations are carried out in industry. In the case of isolated enzymes the cost of enzyme is expected to drop due to an efficient production with genetically engineered microorganisms or higher cells. Rozzell (1999) has discussed myths and realities... 

The use of biocatalysis for the production of chemicals started to receive serious interest in the 1960s with the development of immobilized aminoacylases for the production of chirally pure amino acids by Tanabe Seigaku of Japan, as well as the application of penicillin acylase for the production of 6-aminopenicillanic acid (6-APA), a key... 

Biocatalysis has been very useful in many penicillin transformations, and an interesting comparison between an enzymic process and the corresponding synthetic chemical process is shown in Scheme 1... 

Biotechnological processes can be divided into fermentation processes and biotransformations. In a fermentation process products are formed as primary or secondary metabolites by microorganisms or higher cells from components in the fermentation broth. Product examples are amino acids, vitamins or antibiotics such as penicillin or cephalosporine. In these cases co-solvents are sometimes used for m situ product extraction. The term biotransformation or biocatalysis is used for processes where a starting material (precursor) is converted into the desired product... 

Biocatalysis, as the name suggests, involves using enzymes or other natural catalysts to carry out chemical reactions. This tends to work well within the context of green chemistry since biological reactions are often catalyzed in water at mild temperatures emd pH values. Moreover, enzymes are themselves environmentally benign and obtained from natural sources. In addition to these benefits, biocatalyzed reactions typically proceed with high selectivity emd specificity and require relatively few synthetic steps, thus minimizing the amount of unwanted byproducts produced. Some examples of biocatalyzed syntheses are those of penicillins, cephalosporins (another class of antibiotics). 

The industrial manufacture of semi-synthetic penicillins and cephalosporins is an outstanding example of the integration of chemistry and biocatalysis. The impact of biocatalysis shortens the synthesis for Cefalexin from ten to six steps is a successful example (Fig. 16) [55,56]. 

Bruggink A (2000), Green solutions for chemical challenges biocatalysis in the synthesis of semi-synthetic antibiotics. In Zwanenburg B, Mikolajczyk M, Kielbasinsky P (eds) Enzymes in action. NATO sciences series 1/33, Kluwer Academic, pp 449-458 Bruggink A, Roos EC, de Vroom E (1998) Penicillin acylase in the industrial production of lactam antibiotics.Org Process Res Dev2 128-133... 

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