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Enzymatic Synthesis of Chiral Phenylalanine Derivatives by a Dynamic Kinetic Resolution of Corresponding Amide and Nitrile Substrates with a Multi-Enzyme System

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논문

Enzymatic Synthesis of Chiral Phenylalanine Derivatives by a Dynamic Kinetic Resolution of Corresponding Amide and Nitrile Substrates with a Multi-Enzyme System

학술지

Advanced synthesis & catalysis

저자명

Yasukawa, Kazuyuki; Asano, Yasuhisa

초록

<P><B>Abstract</B></P><P>Mutant &alpha;&#8208;amino&#8208;&epsilon;&#8208;caprolactam (ACL) racemase (L19V/L78T) from <I>Achromobacter obae</I> with improved substrate specificity toward phenylalaninamide was obtained by directed evolution. The mutant ACL racemase and thermostable mutant <SMALL>D</SMALL>&#8208;amino acid amidase (DaaA) from <I>Ochrobactrum anthropi</I> SV3 co&#8208;expressed in <I>Escherichia coli</I> (pACLmut/pDBFB40) were utilized for synthesis of (<I>R</I>)&#8208;phenylalanine and non&#8208;natural (<I>R</I>)&#8208;phenylalanine derivatives (4&#8208;OH, 4&#8208;F, 3&#8208;F, and 2&#8208;F&#8208;Phe) by dynamic kinetic resolution (DKR). Recombinant <I>E. coli</I> with DaaA and mutant ACL racemase genes catalyzed the synthesis of (<I>R</I>)&#8208;phenylalanine with 84% yield and 99% <I>ee</I> from (<I>RS</I>)&#8208;phenylalaninamide (400&#8197;mM) in 22&#8197;h. (<I>R</I>)&#8208;Tyrosine and 4&#8208;fluoro&#8208;(<I>R</I>)&#8208;phenylalanine were also efficiently synthesized from the corresponding amide compounds. We also co&#8208;expresed two genes encoding mutant ACL racemase and <SMALL>L</SMALL>&#8208;amino acid amidase from <I>Brevundimonas diminuta</I> in <I>E. coli</I> and performed the efficient production of various (<I>S</I>)&#8208;phenylalanine derivatives. Moreover, 2&#8208;aminophenylpropionitrile was converted to (<I>R</I>)&#8208;phenylalanine by DKR using a combination of the non&#8208;stereoselective nitrile hydratase from recombinamt <I>E. coli</I> and mutant ACL racemase and DaaA from <I>E. coli</I> encoding mutant ACL racemase and DaaA genes.</P>

발행연도

2012

발행기관

WILEY&#x2010;VCH Verlag

ISSN

1615-4150

ISSN

1615-4169

354

17

페이지

pp.3327-3332

주제어

amidases; amino acids; α&#x2010; amino&#x2010; ε&#x2010; caprolactam racemase; biotransformation; directed evolution; dynamic kinetic resolution;

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1 2023-12-11
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논문; 2012-11-08

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