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Integration of newly isolated biocatalyst and resin-based in situ product removal technique for the asymmetric synthesis of (R)-methyl mandelate

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Abstract

The enantioselective reduction of methyl benzoylformate to (R)-methyl mandelate, an important pharmaceutical intermediate and a versatile resolving agent, was investigated in this study. After minimizing the reaction-specific constraints (constraints dependent on the nature of the substrate and product) by preliminary selection of the reaction parameters, an effective whole cell biocatalyst (Saccharomyces cerevisiae AS2.1392) was obtained by simple screening procedures. Under further optimized conditions, a product concentration of 103 mmol L−1 could be attained within 5 h with a yield of 85.8% and an enantiometric excess of 95.4%, indicating S. cerevisiae AS2.1392 an efficient biocatalyst for the asymmetric synthesis of (R)-methyl mandelate. Furthermore, resin-based in situ product removal (ISPR) technique was applied to alleviate the substrate and product inhibition or toxicity to the whole cells. The integration of newly isolated biocatalyst and proper ISPR technique provides a practical route for the preparation of optically active pharmaceutical intermediates.

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Acknowledgments

The authors gratefully acknowledged the financial support of this work by the National Key Basic Research and Development Program of China (973 program) (2009CB724706), the Hi-Tech Research and Development Program of China (863 Program No. 2007AA02Z226) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT0532).

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  1. Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, 214122, Wuxi, Jiangsu, China

    Jin-Ling Guo, Xiao-Qing Mu & Yan Xu

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  1. Jin-Ling Guo
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  2. Xiao-Qing Mu
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  3. Yan Xu
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Correspondence to Yan Xu.

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Guo, JL., Mu, XQ. & Xu, Y. Integration of newly isolated biocatalyst and resin-based in situ product removal technique for the asymmetric synthesis of (R)-methyl mandelate. Bioprocess Biosyst Eng 33, 797–804 (2010). https://doi.org/10.1007/s00449-009-0401-2

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