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

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1 Department of Biotechnology, School of Bioengineering, Dalian Polytechnic University, Dalian, Liaoning Province, China
2 Department of Chemical Engineering, Tsinghua University, Beijing, China
DOI
10.7287/peerj.preprints.1122v1
Published
Accepted
Subject Areas
Biochemistry, Bioengineering, Biotechnology
Keywords
Penicillin G acylase, kinetically controlled synthesis, polybasic alcohols, co-solvent, cephalexin, biocompatibility, selectivity
Copyright
© 2015 Shi et al.
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
Cite this article
Shi Y, Cao Z, Shen Z. 2015. Impact of polybasic alcohols on biocompatibility and selectivity of Penicillin G Acylase for kinetically controlled synthesis. PeerJ PrePrints 3:e1122v1

Abstract

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.

Author Comment

This is a submission to PLOS ONE for review.