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 catalyst particle caused by conventional impellers, while
preserving a good mixing, Taylor−Couette flow was used. In addition, a convenient biocatalyst matrix was
developed, to allow easy separation between the crystals and the enzyme support. A bench-scale (50 mL)
Taylor vortex flow reactor (VFR), with a radius ratio of η = 0.27 and operating in fed-batch mode, was used
for proof of the concept. To sustain homogeneous fluidization of the biocatalyst, the VFR operated with a
rotational Reynolds number of Re = 5605, within the turbulent Taylor vortices flow region. With this reactor−catalyst ensemble, 100% activity and complete physical integrity of the particles were sustained after 200 h
of operation.