Strategies in the Design of a Penicillin Acylase Process

Abstract

The development of an immobilized enzyme process for commercial application involves a series of steps and compromises, beginning with the selection of the enzyme and its source and ending with the downstream processing to obtain the product in a suitable form. Each step concerns one or various disciplines and is dependent on the other steps influencing the overall economics of the final process. In this paper such a situation is illustrated with the case of the 6aminopenicillanic acid production process. Contributions concerning the production of the enzyme penicillin acylase are described. They involve molecular biology (the construction of a recombinant strain) and bioengineering (the overproduction of the enzyme in an exponentially fed-batch culture). The selection between an enzyme or a whole cell biocatalyst is discussed in terms of its technical and economical consequences. The kinetic behaviour, reactor type and operation strategy are also discussed, showing that specific activity of the biocatalyst and enzyme stability are the key properties affecting the performance of the process and therefore the overall economics. It is also shown that predictions made by modeling and simulation are important to define goals for genetic and protein engineering contributions to the process.