Classical and New Pharmaceutical Uses of Bacterial Penicillin G Acylase

Abstract

Background: β-lactam antibiotics are the most used worldwide for the treatment of bacterial infections. The consumption of these classes of drugs is high, and it is increasing around the world. To date, the best way to produce them is using penicillin G Acylase (PGA) as a biocatalyst. Objective: This manuscript offers an overview of the most recent advances in the current tools to improve the activity of the PGA and its pharmaceutical application. Results: Several microorganisms produce PGA, but some bacterial strains represent the primary source of this enzyme. The activity of bacterial PGA depends on its adequate expression and carbon or nitrogen source, as well as a specific pH or temperature depending on the nature of the PGA. Additionally, the PGA activity can be enhanced by immobilizing it to a solid support to recycle it for a prolonged time. Likewise, PGAs more stable and with higher activity are obtained from bacterial hosts genetically modified. Conclusion: PGA is used to produce b-lactam antibiotics. However, this enzyme has pharmaceutical potential to be used to obtain critical molecules for the synthesis of anti-tumor, antiplatelet, antiemetic, antidepressive, anti-retroviral, antioxidant, and antimutagenic drugs.

Structure-Properties Correlation of Cross-Linked Penicillin G Acylase Crystals

“…Volumetric enzyme activity EA (U/mL) can be calculated using the time-dependent slope of the absorbance dA/dt (min −1 ) according to Equation (5).…”

“…PGAs are ubiquitous; they are found in fungi, yeast and bacteria. In industry, PGAs from Gram-negative bacteria such as Escherichia coli (EcPGA) or Gram-positive bacteria such as Priestia megaterium (formerly known as Bacillus megaterium) (BmPGA) are mainly used [4,5]. Recently, two novel PGAs from Gram-positive Bacillus thermotolerans (BtPGA) and Bacillus sp.…”

Exploitation of E. coli for the production of penicillin G amidase: a tool for the synthesis of semisynthetic β-lactam antibiotics

“…Due to the enormous use of antibiotics, pathogens have developed resistance against them with time. Thus, to overcome this concern, the only method is to synthesize new semisynthetic antibiotics [ 8 ]. The recent efforts for the overproduction of PGA are achieved through genetic engineering by constructing novel recombinant host/vector systems [ 7 ].…”

Degradation of Penicillin G by Visible Light Irradiation-assisted Biotransformation by Whole Cell Paracoccus Sp.

“…Other degradation products, such as amino-penicillanic acid, reversibly synthesizes penicillin and other stable β-lactams [15][16][17]. Furthermore, a thiazole intermediate degradation product has potential environmental pollution risks [18].…”