Enzymatic Synthesis of Enantiopure α- and β-Amino Acids by Phenylalanine Aminomutase-Catalysed Amination of Cinnamic Acid Derivatives

Bian Wu, Wiktor Szymanski, Pieter Wietzes, Stefaan de Wildeman, Gerrit J. Poelarends, Ben L. Feringa, Dick B. Janssen*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

65 Citaten (Scopus)

Samenvatting

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 (1010) cofactor is essential for the PAM-catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.

Originele taal-2English
Pagina's (van-tot)338-344
Aantal pagina's7
TijdschriftChemBioChem
Volume10
Nummer van het tijdschrift2
DOI's
StatusPublished - 26-jan-2009

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