Use of enzyme penicillin acylase in selective amidation/amide hydrolysis to resolve ethyl 3-amino-4-pentynoate isomers

Topgi, Ravindra Satish; Ng, John S.; Landis, Bryan H.; Wang, Ping; Behling, James R.

doi:10.1016/s0968-0896(99)00155-8

Cited by 40 publications

(10 citation statements)

References 52 publications

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“…The resulting pure enantiomers can be used as intermediates for the synthesis of biologically active compounds. For instance, a racemate mixture of ethyl-3-amino-4-pentynoate can be resolved through an enantioselective acylation catalyzed by penicillin G acylase from E. coli to yield the S-isomer, which can be used as a chiral synthon for the synthesis of the anti-platelet agent Xemilofiban (Topgi et al 1999). A recent important application of penicillin G acylase is represented by the kinetic enantioselective acylation of the racemic azetidinone intermediate for the synthesis of the carbacephalosporin antibiotic Loracarbef, an analogue of Cefaclor (Zmijewski et al 1991;Cainelli et al 1997).…”

Section: Biotechnological Applications Of Penicillin Acylasesmentioning

confidence: 99%

Biotechnological applications of penicillin acylases: state-of-the-art

Arroyo

Mata

Acebal

et al. 2003

Appl Microbiol Biotechnol

175

108

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This review describes the most recent developments in the biotechnological applications of penicillin acylases. This group of enzymes is involved mainly in the industrial production of 6-aminopenicillanic acid and the synthesis of semisynthetic beta-lactam antibiotics. In addition, penicillin acylases can also be employed in other useful biotransformations, such as peptide synthesis and the resolution of racemic mixtures of chiral compounds. Particular emphasis is placed on advances in detection of new enzyme specificities towards other natural penicillins, enzyme immobilization, and optimization of enzyme-catalyzed hydrolysis and synthesis in the presence of organic solvents.

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Section: Biotechnological Applications Of Penicillin Acylasesmentioning

confidence: 99%

Biotechnological applications of penicillin acylases: state-of-the-art

Arroyo

Mata

Acebal

et al. 2003

Appl Microbiol Biotechnol

175

108

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“…One of the possible applications of PGA is in amidation reactions, using amines different from the antibiotic nuclei (Topgi et al, 1999; Waldmann et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Thermodynamically Controlled Synthesis of Amide Bonds Catalyzed by Highly Organic Solvent-Resistant Penicillin Acylase Derivatives

Abián¹,

Mateo²,

Fernández‐Lorente³

et al. 2008

Biotechnol Progress

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A study of various direct condensations between different amines, having very high pK values, and unmodified acyl donors has been performed. This has been possible by the use of a very stable PGA derivative. First, it has been found that the higher the cosolvent concentration, the higher the pK of the acyl donor and thus the higher the yield. Therefore, these high concentrations of cosolvents seem to be a requisite for certain enzymatic condensations. Using ethanolamine and 2-hydroxy-2-phenylethyl-amine as nucleophiles and phenyl acetic acid as the acyl donor, the increase in the diglyme concentration from 50 to 90% (v/v) permitted improvement of not only the yield (reaching values higher than 99% in both cases) but also the reaction rates (by 360- or 3-fold, respectively). However, even when using PGA preparations stabilized by multipoint covalent attachment, it was not possible to obtain these results by inactivation of the enzyme derivative. Thus, in the protection of the octylamine with phenylacetic acid in 90% diglyme, the enzymatic activity was more than 20-fold higher using the hydrophilized derivative than the glyoxyl PGA, which allowed us to obtain a yield higher than 99%. Thus, the use of hydrophilized derivatives that are very stable even in the presence of high concentrations of organic solvents opens new opportunities in the use of PGA in organic chemistry.

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“…In particular, the enantioselective resolution of N-phenylacetyl-β-amino acid by Penicillin G amidase has been reported to be highly useful. [4][5][6][7][8] With this method, however, bulky and expensive acylation reagents are required, if the acids are to be recognized by known Nacyl-β-amino acid acylases. One of the most cost-effective acylation methods is acetylation, and enzymatic resolution of N-acetyl-β-amino acids was successful in the industrial production of β-amino acids.…”

mentioning

confidence: 99%

Purification and characterization of enantioselective N-acetyl-β-Phe acylases from Burkholderia sp. AJ110349

Imabayashi

Suzuki

Kawasaki

et al. 2016

Bioscience, Biotechnology, and Biochemistry

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For the production of enantiopure β-amino acids, enantioselective resolution of N-acyl β-amino acids using acylases, especially those recognizing N-acetyl-β-amino acids, is one of the most attractive methods. Burkholderia sp. AJ110349 had been reported to exhibit either (R)- or (S)-enantiomer selective N-acetyl-β-Phe amidohydrolyzing activity, and in this study, both (R)- and (S)-enantioselective N-acetyl-β-Phe acylases were purified to be electrophoretically pure and determined the sequences, respectively. They were quite different in terms of enantioselectivities and in their amino acids sequences and molecular weights. Although both the purified acylases were confirmed to catalyze N-acetyl hydrolyzing activities, neither of them show sequence similarities to the N-acetyl-α-amino acid acylases reported thus far. Both (R)- and (S)-enantioselective N-acetyl-β-Phe acylase were expressed in Escherichia coli. Using these recombinant strains, enantiomerically pure (R)-β-Phe (>99% ee) and (S)-β-Phe (>99% ee) were obtained from the racemic substrate.

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Use of enzyme penicillin acylase in selective amidation/amide hydrolysis to resolve ethyl 3-amino-4-pentynoate isomers

Cited by 40 publications

References 52 publications

Biotechnological applications of penicillin acylases: state-of-the-art

Biotechnological applications of penicillin acylases: state-of-the-art

Thermodynamically Controlled Synthesis of Amide Bonds Catalyzed by Highly Organic Solvent-Resistant Penicillin Acylase Derivatives

Purification and characterization of enantioselective N-acetyl-β-Phe acylases from Burkholderia sp. AJ110349

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