Penicillin amidase

About: Penicillin amidase is a research topic. Over the lifetime, 576 publications have been published within this topic receiving 15563 citations. The topic is also known as: penicillin amidohydrolase & ampicillin acylase.

A substrate susceptivity screening on penicillin amidase

Abstract: INTRODUCTION In the synthesis of p-lactam antibiotics, the application of enzymatic catalysts has become more and more relevant. The steps directly involved in the use of penicillin amidase (PA) in the synthetic pathway to these target molecules are those for the preparation of 6-APA and 7-ADCA, and more recently for the direct synthesis of the exe-cyclic amino bond ~~3.4.5, s). Encouraging results in the latter reaction were reached using penicillin amidases and amino acid hydrolases from various strains. The most frequently used micro-organism is E. co/i, either as a first source of PA or as a producer of amidases cloned from other strains. Penicillin amidases from E. co/i and the phylogenetically related enzymes showed a wide versatility when used as catalysts far from their natural functions. Those enzymes have a fairly constricted substrate susceptivity toward the acyl moiety. The kinetic and mechanistic consequences coming from the structural morphology of the involved molecules were the subject of several publications V. 8. IO. 11). The need to concentrate our efforts on non-sterile approaches to the synthesis of penicillins and cephalosporins led us to develop a quick method to evaluate the “crude” substrate susceptibility of the acyl moieties, by carrying out the reaction between a nucleophilic nucleus (penicillinic or cephalosporanlc) and an activated derivative of aryl acetic acids, by means of hydrolysis rate measurements of the selected derivative. The chosen condition had to allow an evaluation of the relative enzymatic activity expressed over a series of molecules. This parameter provides an indirect evaluation of the acyt moiety fit to the active site of the enzyme, but it does not give conclusive information about the distribution between the products of the reaction with either a nucleophilic group or water p, 31. 13). In experimental systems involving penicillinic or cephalosporanic nuclei, the values of hydrolytic activity allow a first screening of the chances of success in relation to sets of values of the fundamental parameters of the reaction (14, IS).

Biocatalysis in the Chiral Recognition of meso‐Diamides ‐ An Efficient Route from Cyclic Olefinic Hydrocarbons to Optically Pure Diamino‐ Polyols.

Abstract: meso-Diamino-di(tri,tetr)ols 1 – 8 were synthesized starting from cheap carbocyclic olefins and cis -diepoxy derivatives. Enantioselective hydrolysis of the corresponding bis(phenylacet)amides with penicillin amidase from E. coli (EC 3.5.1.11) was effected in good yields (73 – 90%) and with high optical purities (ee 91 − >97).

Molecular Modeling of Penicillin Acylase Binding with a Penicillin Nucleus by High Performance Computing: Can Enzyme or its Mutants Possess beta-lactamase Activity?

Abstract: High-performance computing has been used for molecular modeling of penicillin acylase interaction with a penicillin nucleus 6-aminopenicillanic acid (6-APA) to assess whether the wild-type enzyme or its mutants could possess β-lactamase activity. Applying parallel hybrid GPU/CPU computing technologies for metadynamics calculations with the PLUMED library in conjunction with AMBER software suite it has been shown that trace amounts of wild-type penicillin acylase6-APA complexes leading to a β-lactamase reaction can be formed. Higher β-lactamase activity can be observed in enzyme mutants by introducing charged residue in the substrate binding pocket and its proper positioning with respect to a catalytic nucleophile, including stabilization of the tetrahedral intermediate in the oxyanion hole. Thus, it has been shown that the certain mutations facilitate the orientation of the substrate required for the manifestation of β-lactamase activity in the penicillin acylase active center.

Chemoenzymic Synthesis of Pα-Methyl Deoxynucleoside Triphosphates.

Abstract: 5′-O-(methylphosphonyl)-N-(phenylacetyl)-2 ′-deoxycytidine, deoxyadenosine and deoxyguanosine were pyrophosphorylated and the resulting N-protected P α-methyl nucleoside triphosphates were deblocked by treatment with penicillin amidase at pH 7.8, 25°C to give P α-methyl nucleoside triphosphates.