Efficient Tandem Biocatalytic Process for the Kinetic Resolution of Aromatic β‐Amino Acids

Wu, Bian; Szymański, Wiktor; Wildeman, S. De; Poelarends, Gerrit J.; Feringa, Bernard; Janssen, Dick B.

doi:10.1002/adsc.201000035

Cited by 40 publications

(15 citation statements)

References 29 publications

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“…Recently, a tandem biocatalytic process was described by using the mutase activity of PAM to convert ( R )‐β‐phenylalanine to ( S )‐α‐phenylalanine in combination with PAL to deaminate ( S )‐α‐phenylalanine to cinnamic acid, finally yielding enantiopure ( S )‐β‐phenylalanine 14. As we have found that the Arg92Ser mutation converts PAM into an ammonia lyase accepting ( R )‐β‐phenylalanine, the mutated enzyme was tested for application in the kinetic resolution of rac ‐β‐phenylalanine (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Redesign of a Phenylalanine Aminomutase into a Phenylalanine Ammonia Lyase

et al. 2013

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An aminomutase, naturally catalyzing the interconversion of (S)‐α‐phenylalanine and (R)‐β‐phenylalanine, was converted into an ammonia lyase catalyzing the nonoxidative deamination of phenylalanine to cinnamic acid by a rational single‐point mutation. It could be shown by crystal structures and kinetic data that the flexibility of the lid that covers the active site decides whether the enzyme acts as a lyase or a mutase. An Arg92Ser mutation destabilized the closed conformation of the lid structure and converted the mutase into a lyase that exhibited up to 44‐fold increased reaction rates in the enantioselective deamination of (R)‐β‐phenylalanine. In addition, the amination rates of cinnamic acid yielding optically pure (S)‐α‐ and (R)‐β‐phenylalanine were doubled. The applicability of the mutant enzyme for kinetic resolution and asymmetric amination could be shown by biocatalysis on a preparative scale.

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Section: Resultsmentioning

confidence: 99%

Redesign of a Phenylalanine Aminomutase into a Phenylalanine Ammonia Lyase

et al. 2013

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“…Due to its PAL activity, PAM can be also applied to produce a mixture of (S)--and (R)--arylalanines (51). The combined use of PAM and PAL allows the preparation of (S)--arylalanines from their racemates (52). In this process, PAM isomerizes the (R)--arylalanine and PAL selectively degrades the forming (S)--amino acid.…”

Section: Introductionmentioning

confidence: 98%

Preparation of Unnatural Amino Acids with Ammonia-Lyases and 2,3-Aminomutases

Poppe

Paizs

Kovács

et al. 2011

Methods in Molecular Biology

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Ammonia-lyases catalyze a wide range of processes leading to α,β-unsaturated compounds by elimination of ammonia. In this chapter, ammonia-lyases are reviewed with major emphasis on their synthetic applications in stereoselective preparation of unnatural amino acids. Besides the synthesis of various unnatural α-amino acids with the aid of phenylalanine ammonia-lyases (PALs) utilizing the 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) prosthetic groups, the biotransformations leading to various unnatural β-amino acids with phenylalanine 2,3-aminomutases using the same catalytic MIO prosthetic group are discussed. Cloning, production, purification, and biotransformation protocols for PAL are described in detail.

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“…The production of taxol by Taxus species ( T. chinensis , T. cuspidata , T. wallachiana , and T. canadensis ), andrimid by Pantoea agglomerans , and enedyine C‐1027 chromophore by Streptomyces globisporus indicated that an aromatic 2,3‐aminomutase in the producer organism was necessary to form the β‐amino acid related fragment in these secondary metabolites from the corresponding α‐amino acid. In addition to their role in nature, phenylalanine 2,3‐aminomutases (PAMs) gained increasing synthetic importance in the production of various unnatural β‐arylalanines . PAM catalysis starting from α‐amino acids or racemic β‐amino acids could be applied to produce various unnatural β‐amino acids through kinetic resolution or asymmetric ammonia addition to arylacrylates, even in cascades coupled with isomerization of racemic α‐amino acids in conjunction with a promiscuous racemase .…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas fluorescensStrain R124 Encodes Three Different MIO Enzymes

et al. 2018

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A number of class I lyase-like enzymes, including aromatic ammonia-lyases and aromatic 2,3-aminomutases, contain the electrophilic 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) catalytic moiety. This study reveals that Pseudomonas fluorescens R124 strain isolated from a nutrient-limited cave encodes a histidine ammonia-lyase, a tyrosine/phenylalanine/histidine ammonia-lyase (XAL), and a phenylalanine 2,3-aminomutase (PAM), and demonstrates that an organism under nitrogen-limited conditions can develop novel nitrogen fixation and transformation pathways to enrich the possibility of nitrogen metabolism by gaining a PAM through horizontal gene transfer. The novel MIO enzymes are potential biocatalysts in the synthesis of enantiopure unnatural amino acids. The broad substrate acceptance and high thermal stability of PfXAL indicate that this enzyme is highly suitable for biocatalysis.

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Efficient Tandem Biocatalytic Process for the Kinetic Resolution of Aromatic β‐Amino Acids

Cited by 40 publications

References 29 publications

Redesign of a Phenylalanine Aminomutase into a Phenylalanine Ammonia Lyase

Redesign of a Phenylalanine Aminomutase into a Phenylalanine Ammonia Lyase

Preparation of Unnatural Amino Acids with Ammonia-Lyases and 2,3-Aminomutases

Pseudomonas fluorescensStrain R124 Encodes Three Different MIO Enzymes

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