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

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논문

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

학술지

Biocatalysis and biotransformation

저자명

Seo, Young-Man; Kim, Aran; Bea, Han-Seop; Lee, Sang-Hyeup; Yun, Hyungdon

초록

<P><SMALL>L</SMALL>-6-Hydroxynorleucine was synthesized from 2-keto-6-hydroxyhexanoic acid using branched-chain aminotransferase from <I>Escherichia coli</I> with <SMALL>L</SMALL>-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 <SMALL>L</SMALL>-glutamate by using <SMALL>L</SMALL>-aspartate as an amino donor. On the other hand, pyruvate decarboxylase further shifted the reaction equilibrium towards <SMALL>L</SMALL>-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 <SMALL>L</SMALL>-6-hydroxynorleucine (> 99% <I>ee</I>) was produced from 100 mM 2-keto-6-hydroxyhexanoic acid, whereas in a single branched-chain aminotransferase reaction only 22.5 mM <SMALL>L</SMALL>-6-hydroxynorleucine (> 99% <I>ee</I>) was produced.</P>

발행연도

2012

발행기관

Informa Healthcare

ISSN

1024-2422

ISSN

1029-2446

30

2

페이지

pp.171-176

주제어

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

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논문; 2012-12-31

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