Enzymes in the pharmaceutical industry for β-lactam antibiotic production

Beta-lactam antibiotics are the largest family of antimicrobial agents and the most widely used in current clinical practice. Moreover, antibiotics are the most important products of biotechnology and semisynthetic penicillins and cephalosporins represent more than 60% of total antibiotic sales with estimated annual sales of $15 billion and a production volume of 37,000 tons per year. For this reason, the optimization of its production is a challenge. Even when beta-lactam antibiotics are conventionally manufactured using chemical synthetic routes, enzyme biocatalysis of these antibiotics has slowly displaced chemical synthesis, not only because of economic considerations but also to severely reduce wastes and produce less hazardous effluent contaminants to comply with the principles of green chemistry. In addition, enzymatic synthesis has permitted the synthesis of potentially effective β-lactam antibiotics (BLAs) as well as more effective β-lactamase inhibitors. In this chapter, we expose the main enzymes used for BLA production and aspects about the optimization process such as time, temperature, enzyme concentration, use of different substrates, immobilization, and other strategies proposed for increasing process effectiveness. The synthesis of novel substituted beta-lactams and structural modifications, genes, enzyme structures, and recombinant enzyme technology will also be discussed.