Enzymatic Synthesis of Enantiopure α- and β-Amino Acids by Phenylalanine Aminomutase-Catalysed Amination of Cinnamic Acid Derivatives
| Autor: | Dick B. Janssen, Stefaan Marie André De Wildeman, Wiktor Szymanski, Gerrit J. Poelarends, Ben L. Feringa, Pieter Wietzes, Bian Wu |
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| Přispěvatelé: | Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Medicinal Chemistry and Bioanalysis (MCB), Synthetic Organic Chemistry, Biotechnology |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
phenylalanine aminomutase
MECHANISM EXPRESSION Stereochemistry phenylalanine HISTIDINE AMMONIA-LYASE enzymes Gene Expression Phenylalanine Biochemistry Cinnamic acid Substrate Specificity chemistry.chemical_compound Ammonia Escherichia coli Organic chemistry CRYSTAL-STRUCTURE BIOSYNTHESIS Enantiomeric excess Intramolecular Transferases Molecular Biology Amination chemistry.chemical_classification BIOCATALYSIS biology Organic Chemistry TYROSINE AMINOMUTASE Imidazoles Regioselectivity Active site Stereoisomerism PEPTIDES Amino acid SUBSTRATE-SPECIFICITY ammonia lyase chemistry Cinnamates Biocatalysis ESCHERICHIA-COLI biology.protein Molecular Medicine Taxus |
| Zdroj: | ChemBioChem, 10(2), 338-344. WILEY-V C H VERLAG GMBH |
| ISSN: | 1439-4227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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