Penicillin G Acylase: Its Synthesis, Regulation, and Production

Overview

Pencilin G acylase (PGA) is one of very important industrial enzymes used in the production of polysynthetic R-lactam antibbottks. This enzyme catalyzes the hydrolysis of the amidic bond of penicillin G with the development of 6-aminopenicillanic acid which serves as the initial substance for the production of semisynthetic penicillins. In the strain Escherichia coli W ATCC 11105 and ATCC 9637, PGA is coded by the pga gene on the chromozóme and synthesized as the pre-pro-PGA (pp PGA) precursor, which is transportnd, with probable participation of the chaperon system, to the periplasmatic space of the cell. Here after a series of proteolytic reactions the active enzyme PGA develops, consisting of two subunits a and R. Expression of the pga gene is subject to several regulatory mechanisms: temperature repression, catabolic repression by glucose, repression by oxygen, and induction by phenylacetic acid (FOK). The formation of active PGA is also influenced at the post-translation level, where an important role is played by intracellular proteolytic reactions and the transport system of pre-pro-PGA across the cytoplasmatic membrane. The chromozomal area of the pga gene of the E. coli W strain was employed for the construction of many recombinant plasmids. These plasmids served to transprm suitable host strains, some of which are now used in industry as highly productioe microorganisms.

Key words:
penicillin G acylase - synthesis - production strains - plasmids