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Enhanced Dissolution of 7-ADCA in the Presence of PGME for Enzymatic Synthesis of Cephalexin

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Abstract

Enzymatic catalysis has been recognized as a green alternative to classical chemical route for synthesis of cephalexin (CEX). However, its industrial practice has been severely limited by the low productivity due to the low solubility of 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and high hydrolysis of D-phenylglycine methyl ester (PGME). In this work, the enhanced dissolution of 7-ADCA in the presence of PGME for efficient enzymatic synthesis of CEX was investigated. Results showed that the solubility of 7-ADCA in water could be improved by PGME. Moreover, supersaturated solution of 7-ADCA could be created in the presence of PGME by a pH shift strategy. The supersaturated solution of 7-ADCA possess good stability, which could be explained in terms of the inhibition of 7-ADCA precipitation due to the presence of PGME. The interaction between 7-ADCA and PGME is explored by spectroscopic determination and DFT analysis and the mechanism of enhanced dissolution of 7-ADCA in the presence of PGME is discussed and proposed. The feasibility of supersaturated solution of 7-ADCA for the enzymatic synthesis of CEX is evaluated. It was demonstrated that high conversion ratio (> 95.0%) and productivity (> 240.0 mmol/L/h) was obtained under a wide range of reaction conditions, indicating that the supersaturated solution system was highly superior to conventional homogeneous solution system. The information obtained in this work will be helpful to industrial production of CEX via enzymatic route.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work is supported by the National Key R&D Program of China (No. 2021YFC2101000) and Research and Application Service Platform Project of API Manufacturing Environmental Protection and Safety Technology in China (No. 2020–0107-3–1).

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Authors and Affiliations

  1. CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China

    Yixiao Fan, Yingbo Li & Qingfen Liu

  2. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China

    Yixiao Fan

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  1. Yixiao Fan
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  2. Yingbo Li
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Contributions

Conceptualization, methodology, investigation, data curation, formal analysis, writing-original draft, writing-review, and editing were performed by Yixiao Fan. Methodology, formal analysis, writing-review, and editing were performed by Yingbo Li. Funding acquisition, project administration, resources, supervision, validation, writing-review, and editing were performed by Qingfen Liu.

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Correspondence to Yingbo Li or Qingfen Liu.

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Fan, Y., Li, Y. & Liu, Q. Enhanced Dissolution of 7-ADCA in the Presence of PGME for Enzymatic Synthesis of Cephalexin. Appl Biochem Biotechnol 194, 1682–1698 (2022). https://doi.org/10.1007/s12010-021-03705-7

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