Nonconventional Reactor for Enzymatic Synthesis of Semi-Synthetic β-Lactam Antibiotics

The enzymatic synthesis of β-lactam semi-synthetic antibiotics has been receiving increasing attention as a green-chemistry alternative for the industrial production of these drugs, because mild reaction conditions may be used. A nonconventional fed-batch reactor is presented here, using a bi-disperse gel matrix for immobilization of the enzyme penicillin G acylase (PGA) [EC 3.5.1.11]. The catalyst particles are suspended within Taylor−Couette vortices, performing the kinetically controlled synthesis of ampicillin (AMP) from phenylglycine methyl ester (PGME) and 6-aminopenicillanic acid (6-APA). This is a serial−parallel set of reactions, where the desired product (AMP) is the intermediate species, and a high selectivity is essential for the process economics. With this objective, AMP should be precipitated, withdrawing the antibiotic from the liquid phase and reducing its hydrolysis. One key point is to protect the physical integrity of the catalyst within this environment. To avoid damages to the cataly...