Title:
Engineered Amine Dehydrogenases And Methods Of Use Thereof
Engineered Amine Dehydrogenases And Methods Of Use Thereof
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Abstract
Non-naturally occurring amine dehydrogenases (AmDH) and methods of use thereof the produce chiral amines are disclosed. The AmDH are variants of amino acid dehydrogenases. AmDH based on phenylalanine, leucine, and valine scaffolds are provided. The AmDH typically have one, two, three, four, or more amino acid alterations relative to the scaffold. The alterations to the scaffold result in an enzyme that accepts the analogous ketone, such as methyl isobutyl ketone (MIBK), instead of the wild-type α-keto acid. Chimeric AmDH are also disclosed. The chimeras are fusion proteins that include a substrate binding domain from a first AmDH and a cofactor binding domain from a second AmDH. In a preferred embodiment, one of the domains is from a PheDH-based AmDH and one of the domains is from a LeuDH-based AmDH.
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9/16/2014
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Patent