Protein Engineering of Penicillin Acylase

Тишков, В. И.; Савин, С. С.; Yasnaya, A. S.

doi:10.32607/20758251-2010-2-3-47-61

Cited by 24 publications

(14 citation statements)

References 60 publications

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“…2 & Table G in S1 File ), an enzyme that hydrolyzes penicillin G into 6-aminopenicillanate [ 60 ]. The primary physiological role of the penicillin acylase in bacteria is believed to involve the utilization of aromatic amides as carbon sources; penicillins are in fact amidic compounds [ 61 ]. Even though penicillin acylases are used in the industry to develop antibiotics, the enzyme is not part of the normal β-lactams biosynthesis in fungi or bacteria [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

et al. 2015

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Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes.

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Section: Resultsmentioning

confidence: 99%

Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

et al. 2015

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“…The growing emergence and spread of pathogens resistant to antimicrobial drugs, especially to their natural variants, are a growing concern. This reflects the relevance of the search for new antibacterial therapeutics with rare functional groups or with a non-natural core structure, since the resistance of microorganisms to these develops much more slowly [ 80 , 81 , 82 , 83 ]. New data on the antimicrobial action of o -benzoic sulfimide indicates the prospects of this compound as a basis for creating a whole group of new antibacterial isothiazolidine derivatives for the pharmaceutical, food, and agricultural industries.…”

Section: Discussionmentioning

confidence: 99%

To a Question on the Mechanism of the Antimicrobial Action of Ortho-Benzoic Sulfimide

Kasap

Grishin

2020

Pharmaceuticals

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The article summarizes and compares data on the properties and biological activity of o-benzoic sulfimide and sulfanilamide compounds. Attention is given to the biochemical conditions under which o-benzoic sulfimide and sulfanilamides have similar activity groups. The results of the experimental and theoretical studies aimed at understanding the molecular organization and biological activity of folic acid and its homologous complexes are analyzed. A hypothesis about the possible mechanisms of the formation of such complexes with the participation of o-benzoic sulfimide is presented. The perspectives for the use of o-benzoic sulfimide and its homologues in biomedicine are evaluated.

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“…Polybasic alchols for synthesis by PGA 5 superfamily [6]. Protein engineering or directed evolution studies have been used to understand the structure-function relationship and to improve PGA properties such as activity, substrate specificity and stability [7][8][9][10][11][12][13][14][15][16].…”

Section: Preprintsmentioning

confidence: 99%

Impact of polybasic alcohols on biocompatibility and selectivity of Penicillin G Acylase for kinetically controlled synthesis

Shi

Zhu-an

Shen

2015

Preprint

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The enzyme catalyzed synthesis of cephalexin (CEX) from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and D-a-phenylglycine methyl ester (PGM) by Penicillin G acylase (PGA) is a model for kinetically controlled synthesis. The parallel hydrolysis of PGM, the activated acyl donor, is the principle competing pathway in this reaction, limiting the synthetic yield and reaction efficiency. To improve the performance of PGA catalyzed CEX synthesis, the biocompatibility and selectivity of various co-solvents were investigated. Polybasic alcohols such as ethylene glycol, glycerol and PEG400 did not cause deleterious changes to the enzyme, whereas monobasic alcohols, such as butyl alcohol, disrupted the PGA activity. Compared with the reaction in aqueous medium, the use of ethylene glycol as a co-solvent was found to have good selectivity in order to facilitate CEX synthesis and significantly minimize PGM hydrolysis. The pH of ethylene glycol medium was also optimized. The mechanism of the enhanced effect of polybasic alcohols as co-solvents on both biocompatibility and selectivity of enzymatic kinetically controlled synthesis is suggested.

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Protein Engineering of Penicillin Acylase

Abstract: Penicillin acylases (PA) are widely used for the production of semi-synthetic β-lactam antibiotics and chiral compounds. In this review, the latest achievements in the production of recombinant enzymes are discussed, as well as the results of PA type G protein engineering.

Cited by 24 publications

References 60 publications

Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

To a Question on the Mechanism of the Antimicrobial Action of Ortho-Benzoic Sulfimide

Impact of polybasic alcohols on biocompatibility and selectivity of Penicillin G Acylase for kinetically controlled synthesis

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