Phenylalanine Ammonia Lyase Catalyzed Synthesis of Amino Acids by an MIO‐Cofactor Independent PathwayCitation formats

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Phenylalanine Ammonia Lyase Catalyzed Synthesis of Amino Acids by an MIO‐Cofactor Independent Pathway. / Lovelock, Sarah; Lloyd, Richard C.; Turner, Nicholas (Corresponding).

In: Angewandte Chemie - International Edition, Vol. 53, No. 18, 25.04.2014, p. 4652-4656.

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Lovelock, S, Lloyd, RC & Turner, N 2014, 'Phenylalanine Ammonia Lyase Catalyzed Synthesis of Amino Acids by an MIO‐Cofactor Independent Pathway', Angewandte Chemie - International Edition, vol. 53, no. 18, pp. 4652-4656. https://doi.org/10.1002/anie.201311061

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Author

Lovelock, Sarah ; Lloyd, Richard C. ; Turner, Nicholas. / Phenylalanine Ammonia Lyase Catalyzed Synthesis of Amino Acids by an MIO‐Cofactor Independent Pathway. In: Angewandte Chemie - International Edition. 2014 ; Vol. 53, No. 18. pp. 4652-4656.

Bibtex

@article{e4252f442dfa4853821e71ee9e8f8edc,
title = "Phenylalanine Ammonia Lyase Catalyzed Synthesis of Amino Acids by an MIO‐Cofactor Independent Pathway",
abstract = "Phenylalanine ammonia lyases (PALs) belong to a family of 4-methylideneimidazole-5-one (MIO) cofactor dependent enzymes which are responsible for the conversion of L-phenylalanine into trans-cinnamic acid in eukaryotic and prokaryotic organisms. Under conditions of high ammonia concentration, this deamination reaction is reversible and hence there is considerable interest in the development of PALs as biocatalysts for the enantioselective synthesis of non-natural amino acids. Herein the discovery of a previously unobserved competing MIO-independent reaction pathway, which proceeds in a non-stereoselective manner and results in the generation of both L- and D-phenylalanine derivatives, is described. The mechanism of the MIO-independent pathway is explored through isotopic-labeling studies and mutagenesis of key active-site residues. The results obtained are consistent with amino acid deamination occurring by a stepwise E1 cB elimination mechanism.",
author = "Sarah Lovelock and Lloyd, {Richard C.} and Nicholas Turner",
year = "2014",
month = "4",
day = "25",
doi = "10.1002/anie.201311061",
language = "English",
volume = "53",
pages = "4652--4656",
journal = "Angewandte Chemie, International Edition",
issn = "1433-7851",
publisher = "John Wiley & Sons Ltd",
number = "18",

}

RIS

TY - JOUR

T1 - Phenylalanine Ammonia Lyase Catalyzed Synthesis of Amino Acids by an MIO‐Cofactor Independent Pathway

AU - Lovelock, Sarah

AU - Lloyd, Richard C.

A2 - Turner, Nicholas

PY - 2014/4/25

Y1 - 2014/4/25

N2 - Phenylalanine ammonia lyases (PALs) belong to a family of 4-methylideneimidazole-5-one (MIO) cofactor dependent enzymes which are responsible for the conversion of L-phenylalanine into trans-cinnamic acid in eukaryotic and prokaryotic organisms. Under conditions of high ammonia concentration, this deamination reaction is reversible and hence there is considerable interest in the development of PALs as biocatalysts for the enantioselective synthesis of non-natural amino acids. Herein the discovery of a previously unobserved competing MIO-independent reaction pathway, which proceeds in a non-stereoselective manner and results in the generation of both L- and D-phenylalanine derivatives, is described. The mechanism of the MIO-independent pathway is explored through isotopic-labeling studies and mutagenesis of key active-site residues. The results obtained are consistent with amino acid deamination occurring by a stepwise E1 cB elimination mechanism.

AB - Phenylalanine ammonia lyases (PALs) belong to a family of 4-methylideneimidazole-5-one (MIO) cofactor dependent enzymes which are responsible for the conversion of L-phenylalanine into trans-cinnamic acid in eukaryotic and prokaryotic organisms. Under conditions of high ammonia concentration, this deamination reaction is reversible and hence there is considerable interest in the development of PALs as biocatalysts for the enantioselective synthesis of non-natural amino acids. Herein the discovery of a previously unobserved competing MIO-independent reaction pathway, which proceeds in a non-stereoselective manner and results in the generation of both L- and D-phenylalanine derivatives, is described. The mechanism of the MIO-independent pathway is explored through isotopic-labeling studies and mutagenesis of key active-site residues. The results obtained are consistent with amino acid deamination occurring by a stepwise E1 cB elimination mechanism.

U2 - 10.1002/anie.201311061

DO - 10.1002/anie.201311061

M3 - Article

VL - 53

SP - 4652

EP - 4656

JO - Angewandte Chemie, International Edition

JF - Angewandte Chemie, International Edition

SN - 1433-7851

IS - 18

ER -