Effects of ethylene glycol on the synthesis of ampicillin using immobilized penicillin G acylase

Abstract

The effects of organic cosolvents on the synthesis of ampicillin from phenylglycine methyl ester (PGME) and 6-amino penicillanic acid (6-APA) using immobilized Bacillus megaterium penicillin G acylase have been examined. Several cosolvents were tested for their influence on the enzyme in terms of enzyme stability and hydrophobicity. Among the cosolvents tested, ethylene glycol was found to increase the yield of ampicillin by 39-50%. The effects of ethylene glycol on the pK a of PGME, the hydrolysis of ampicillin and PGME, and synthetase/amidase and esterase/amidase ratios were also studied. Experimental data indicated that ethylene glycol inhibited more the hydrolysis of the ampicillin than the hydrolysis of the PGME and the synthetase/amidase ratio varied from 0.2 to 0.88 when the concentration (v/v) of the cosolvent increased from 0 to 40%. The enhancement of the synthesis yield was mainly caused by the reduction in the hydrolysis of acyl donor (PGME) and product (ampicillin) in the water-cosolvent system.

Enzymatic Synthesis of Amoxicillin via a One-pot Enzymatic Hydrolysis and Condensation Cascade Process in the Presence of Organic Co-solvents

“…Recently, there are some reports concerning enzymatic synthesis of β-lactam antibiotics in organic media or water and cosolvent mixture [23][24][25][26][27][28][29][30][31]. The presence of organic solvents can enhance the performance of enzyme, at the same time depress the hydrolysis of products obviously, and thus high synthesis yield can be expected.…”

“…Enzyme activity was also inhibited at high organic solvent concentration. For enzymatic synthesis of β-lactam antibiotics under kinetic control, Illanes [28][29][30] and Wei [31] both reported that EG inhibited the hydrolysis of ampicillin and D-PGM, thus the synthesis yield of the ampicillin could be improved. Sixty percent (v/v) EG in the reaction mixture was selected as the optimal cosolvent content in the further experiments.…”

“…Among these cosolvents, ethylene glycol was used most widely and exhibited some advantages as a cosolvent in the synthesis of β-lactam antibiotics. Illanes et al [28][29][30] and Wei [31] have studied thoroughly the synthesis of cephalexin and ampicillin in the presence of EG. However, there is no report about the use of cosolvents in the enzymatic one-pot synthesis of amoxicillin, and the efficiency should be studied.…”

Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

“…The immobilizing technique of enzymes, including the design of support materials and immobilization methods, is a significant topic in the application field of biocatalysts for at all times [3]. The penicillin G acylase (PGA) has played a key role in the manufacture of semi-synthetic antibiotics because it is capable of catalyzing the hydrolysis of penicillin G to produce 6-aminopenicillanic acid (6-APA) and the acylation of 6-APA to synthesize semisynthetic penicillins [4][5][6]. Now much effort to develop newer type of supports is in progress with the goal of improving the catalytic efficiency of enzyme and reducing the cost of support.…”

Investigation of the solid state properties of amoxicillin trihydrate and the effect of powder pH

“…Also, various hydrated forms of amoxicillin, including monohydrate, dihydrate, and trihydrate, have been reported, among which, the trihydrate is the most stable hydrated form. [6][7][8][9][10][11] Crystallization of AMT, like the other crystalline drugs, plays a critical role in controlling the crystal form, shape, size, and size distribution. Moreover, this process influences the solid state properties and the type of presented impurity in AMT powder.…”