Enzymatic synthesis of enantiopure alpha- and beta-amino acids by phenylalanine aminomutase-catalysed amination of cinnamic acid derivatives.

Chembiochem : a European Journal of Chemical Biology
Bian WuDick B Janssen

Abstract

The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of alpha-phenylalanine to beta-phenylalanine, an important step in the biosynthesis of the N-benzoyl phenylisoserinoyl side-chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)-cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring-substituted (E)-cinnamic acids can serve as a substrate in PAM-catalysed ammonia addition reactions for the biocatalytic production of several important beta-amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non-natural aromatic alpha- and beta-amino acids in excellent enantiomeric excess (ee >99 %). The internal 5-methylene-3,5-dihydroimidazol-4-one (MIO) cofactor is essential for the PAM-catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.

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Citations

Oct 19, 2011·Applied Microbiology and Biotechnology·Hans RajGerrit J Poelarends
Nov 29, 2011·Applied Microbiology and Biotechnology·U EngelJ Rudat
Apr 14, 2011·Chemical Communications : Chem Comm·Han-Seop BeaHyungdon Yun
Nov 3, 2010·Protein Engineering, Design & Selection : PEDS·Sebastian Bartsch, Uwe T Bornscheuer
Mar 1, 2012·Current Opinion in Chemical Biology·Heather L Condurso, Steven D Bruner
Apr 12, 2011·Trends in Biotechnology·Bian WuDick B Janssen
Jul 22, 2009·Current Opinion in Chemical Biology·Heather A CookeSteven D Bruner
Mar 5, 2010·Journal of Separation Science·Salinda WijeratneKevin D Walker
Feb 13, 2014·Angewandte Chemie·Bettina M NestlBernhard Hauer
Dec 7, 2010·Current Opinion in Chemical Biology·Nicholas J Turner
Apr 6, 2013·Current Opinion in Chemical Biology·Matthew M HeberlingDick B Janssen
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May 13, 2017·Chemical Reviews·Fabio ParmeggianiNicholas J Turner
Jan 25, 2018·Chemical Society Reviews·Ya-Ping XueYu-Guo Zheng
Dec 2, 2017·Chembiochem : a European Journal of Chemical Biology·Pál CsukaLászló Poppe

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