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Alpha-amino acid ester hydrolases: Properties and applications

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Abstract

The review describes two major groups of α-amino acid ester hydrolases (AEHs)—enzymes with a similar active center structure, which determines their unique specificity to esters containing an amino group in the α position to the carbonyl. The first group comprises microbial AEHs of the β-lactam acylase type. Technical biocatalysts based on this group of enzymes are used for the production of semi-synthetic amino-β-lactam antibiotics. The second AEH group includes eukaryotic valacyclovirases, which activate in vivo a number of antiviral and anticancer prodrugs. The directed activity of these enzymes is used for the development of target pharmaceutical preparations for the therapy of viral and oncological diseases. The review summarizes and compares the available data on the structure and properties, substrate specificity, and the kinetic parameters of enzymes of these two groups. Experiments identifying the AEH active site and providing the molecular basis for the unique specificity of these enzymes are discussed. The data from the available scientific and patent publications concerning the aminopenicillin and aminocephalosporin synthesis catalyzed by β-lactam acylase AEHs are reviewed and systematized.

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Abbreviations

AEH:

α-amino acid ester hydrolase

7-ADCA:

7-aminodesacetoxycephalosporanic acid

6-APA:

6-aminopenicillanic acid

7-ACA:

7-aminocephalosporanic acid

D-PG:

D-phenylglycine

D-HPG:

D-p-hydroxyphenylglycine

BPHL:

biphenyl hydrolase-like protein

VACV:

valacyclovir

VACVase:

valacyclovirase

hVACVase, rVACVase:

human or rat valacyclovirase, respectively

k cat :

catalytic constant

Km :

Michaelis constant

PEG:

polyethylene glycol

CLEAs:

cross-linked enzyme aggregates

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  1. Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, 117545, Russia

    V. B. Kurochkina, A. V. Sklyarenko, O. V. Berezina & S. V. Yarotskii

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  1. V. B. Kurochkina
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  2. A. V. Sklyarenko
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  3. O. V. Berezina
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Correspondence to A. V. Sklyarenko.

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Original Russian Text © V.B. Kurochkina, A.V. Sklyarenko, O.V. Berezina, S.V. Yarotskii, 2012, published in Biotekhnologiya, 2012, No. 5, pp. 8–37.

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Kurochkina, V.B., Sklyarenko, A.V., Berezina, O.V. et al. Alpha-amino acid ester hydrolases: Properties and applications. Appl Biochem Microbiol 49, 672–694 (2013). https://doi.org/10.1134/S0003683813080036

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