Asymmetric synthesis of L-6-hydroxynorleucine from 2-keto-6-hydroxyhexanoic acid using a branched-chain aminotransferase

作者：Seo Young Man; Kim Aran; Bea Han Seop; Lee Sang Hyeup^*; Yun Hyungdon

来源：Biocatalysis and Biotransformation, 2012, 30(2): 171-176.

DOI：10.3109/10242422.2011.638373

• aminotransferase
• branched-chain aminotransferase
• coupling reaction
• L-6-hydroxynorleucine
• unnatural amino acid

L-6-Hydroxynorleucine was synthesized from 2-keto-6-hydroxyhexanoic acid using branched-chain aminotransferase from Escherichia coli with L-glutamate as an amino donor. Since the branched-chain aminotransferase was severely inhibited by 2-ketoglutarate, the branched-chain aminotransferase reaction was coupled with aspartate aminotransferase and pyruvate decarboxylase. Aspartate aminotransferase converted the inhibitory 2-ketoglutarate back to L-glutamate by using L-aspartate as an amino donor. On the other hand, pyruvate decarboxylase further shifted the reaction equilibrium towards L-6-hydroxynorleucine through decarboxylation of pyruvate to acetaldehyde. The concerted action of the three enzymes significantly enhanced the yield compared to that of branched-chain aminotransferase alone. In the coupled reaction, 90.2 mM L-6-hydroxynorleucine (%26gt; 99% ee) was produced from 100 mM 2-keto-6-hydroxyhexanoic acid, whereas in a single branched-chain aminotransferase reaction only 22.5 mM L-6-hydroxynorleucine (%26gt; 99% ee) was produced.

• 出版日期2012-3