Semisynthetic β-lactum antibiotics, like penicillins are one of the most prescribed categories of antibiotics in the world. They constitute the four membered β-lactum rings, which is an important component to fight bacterial infections, as it prevents cell wall synthesis in the bacteria.
These compounds are categorized as semisynthetic, as their acyl side chain is generated from a chemoenzymatic, or chemical synthesis, and theirs β-component is generated from the hydrolysis of a natural fermentation product.
The β-lactum component for all the penicillins, 6-APA (6-aminopenicillanic acid), is obtained on an industrial scale, by the hydrolysis of either penicillin-V using penicillin G acylase, or by penicillin G using penicillin-G acylase.
The chemical coupling of an acyl side chain with the β-lactum component has ruled the industrial generation of semisynthetic β-lactum antibiotics, even though the procedure needs highly reactive agents, low temperatures, large volume of solvents, and generates huge concentration of waste.
The enzymatic coupling of an acyl side chain with the β-lactum component can be achieved in an environmentally friendly procedure at ambient temperature, in which no hazardous or toxic reagents are required, and therefore reduces waste production.
The production of ampicillin catalyzed by penicillin acylase was enhanced in an aqueous with partly dissolved antibiotic 6-APA. The yields of both acyl donor and 6-APA could be enhanced by spontaneously adding substrates to the reaction, which permits the amount of 6-APA to remain throughout saturated.
In this method of reaction, with four succeeding substrate addition, 72 percent of D-phenyl glycine methyl ester and 97 percent of 6-APA to ampicillin can be obtained. The synthetic tendency of this method was predicted by using a mathematical model. This model showed that by enhancing the concentration of added substrates, the conversion of acyl donor and 6-APA into ampicillin can be obtained.