Abstract
l-2-Aminobutyric acid (l-ABA) is an unnatural amino acid that is a key intermediate for the synthesis of several important drugs. It can be produced by transaminase or dehydrogenase from α-ketobutyric acid, which can be synthesized enzymatically from the bulk amino acid, l-threonine. Deamination of l-threonine followed by a hydrogenation reaction gave almost the theoretical yield and was estimated to be more cost-effective than the established chemical process. l-Threonine deaminase from Escherichia coli, l-leucine dehydrogenase from Bacillus cereus, and formate dehydrogenase from Pseudomonas sp. were over-expressed in E. coli and used for one-pot production of l-ABA with formate as a co-substrate for NADH regeneration. 30 mol l-threonine were converted to 29.2 mol l-ABA at 97.3 % of theoretical yield and with productivity of 6.37 g l−1 h−1 at 50 l. This process offers a promising approach to fulfil industrial requirements for l-ABA.
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Acknowledgments
This work was supported by the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-G-7-1), Hi-Tech industrialized seed fund projects by Pudong New Area and Chinese Academy of Sciences (No. PKC2010-03), and Zhejiang province biocatalytic Engineering Technology Research Center Project (2011E10025). This work was also supported in part by National Basic Research Program of China (973: 2007CB707803, 2011CBA00806), Academy-Locality cooperation program of Chinese Academy of Sciences (DBSH-2011-046), and “365” Outstanding Scientific and Technological Innovation Team of Huzhou (2010KC01). We thanks for the exhaustive discussion with Dr. Bo Wang from gyrochem.
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Rongsheng Tao and Yu Jiang have contributed equally to this work.
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Tao, R., Jiang, Y., Zhu, F. et al. A one-pot system for production of l-2-aminobutyric acid from l-threonine by l-threonine deaminase and a NADH-regeneration system based on l-leucine dehydrogenase and formate dehydrogenase. Biotechnol Lett 36, 835–841 (2014). https://doi.org/10.1007/s10529-013-1424-y
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DOI: https://doi.org/10.1007/s10529-013-1424-y