Current state and perspectives of penicillin G acylase-based biocatalyses

Abstract

In the course of more than 60-year history, penicillin G acylase (PGA) gained a unique position among enzymes used by pharmaceutical industry for production of β-lactam antibiotics. Kinetically controlled enzymatic syntheses of cephalosporins of novel generations in which PGA catalyzes coupling of activated acyl donor with nucleophile belong among the latest large-scale applications. Contrary to rather specific roles of other enzymes involved in β-lactam biocatalyses, the PGA seems to have the greatest potential. On the laboratory scale, other applications with industrial potential were described, e.g., directed evolution of the enzyme to meet specific demands of industrial processes or its modification into the enzyme catalyzing reactions with novel substrates. The fact that β-lactams represent the most important group of antibiotics comprising 65 % of the world antibiotic market explains such a tremendous and continuous interest in this enzyme. Indeed, the annual consumption of PGA has recently been estimated to range from 10 to 30 million tons. The application potential of the enzyme goes beyond the β-lactam biocatalysis due to its enantioselectivity and promiscuity: the PGA can be used for the production of achiral and chiral compounds convenient for the preparation of synthons and active pharmaceutical ingrediences, respectively. These biocatalyses, however, still wait for large-scale application.

Facile immobilization of enzyme on three dimensionally ordered macroporous silica via a biomimetic coating

“…27 Nowadays, much work is still being done to search for novel immobilization techniques and new support materials. 28,29 Thus, in this work, PGA was chosen as a model enzyme to address the possibility of using 3DOM silica as a carrier and norepinephrine as a multifunctional surface modification reagent to realize enzyme immobilization. To the best of our knowledge, this is the first time the feasibility of immobilizing enzyme on 3DOM silica via a biomimetic coating is explored.…”

Design and synthesis study of the thermo‐sensitive copolymer carrier of penicillin G acylase

“…Immobilized penicillin G acylase (PGA) has been widely used in the process of the catalyzing hydrolysis of penicillin G potassium to produce 6‐aminopenicillanic acid (6‐APA) . Driven by the intensive and extensive application evolution, researchers have found that the properties of carriers play a key role in immobilized PGA, not only influence the activity of PGA at a large state, but also decide the loading amount, response rate, and recovery of PGA directly …”

Penicillin acylase-catalyzed synthesis of N-bromoacetyl-7-aminocephalosporanic acid, the key intermediate for the production of cefathiamidine

“…Currently, the large-scale enzymatic production of many semi-synthetic β-lactam antibiotics such as cephalexin has been realized with PAs as biocatalysts (Wegman et al 2001; Bruggink et al 1998). Compared to chemical methods, the enzymatic routes appear to be preferable for the synthesis of semi-synthetic β-lactam antibiotics because of many advantages such as mild reaction conditions, avoiding use of toxic chemicals, producing less waste, and being simple and environmentally friendly (Arroyo et al 2003; Bruggink et al 1998; Marešová et al 2014). However, to our knowledge, enzymatic or chemoenzymatic synthesis of cefathiamidine has not been reported yet.…”