Discovery of two cyanobacterial phenylalanine ammonia lyases: kinetic and structural characterization.

Phenylalanine ammonia lyase (PAL) catalyzes the deamination of phenylalanine to cinnamate and ammonia. While PALs are common in terrestrial plants where they catalyze the first committed step in the formation of phenylpropanoids, only a few prokaryotic PALs have been identified to date. Here we describe for the first time PALs from cyanobacteria, in particular, Anabaena variabilis ATCC 29413 and Nostoc punctiforme ATCC 29133, identified by screening the genome sequences of these organisms for members of the aromatic amino acid ammonia lyase family. Both PAL genes associate with secondary metabolite biosynthetic gene clusters as observed for other eubacterial PAL genes. In comparison to eukaryotic homologues, the cyanobacterial PALs are 20% smaller in size but share similar substrate selectivity and kinetic activity toward L-phenylalanine over L-tyrosine. Structure elucidation by protein X-ray crystallography confirmed that the two cyanobacterial PALs are similar in tertiary and quatenary structure to plant and yeast PALs as well as the mechanistically related histidine ammonia lyases.

[1]  M. Bowman,et al.  Structural determinants and modulation of substrate specificity in phenylalanine-tyrosine ammonia-lyases. , 2006, Chemistry & biology.

[2]  R. Müller,et al.  Genes and Enzymes Involved in Caffeic Acid Biosynthesis in the Actinomycete Saccharothrix espanaensis , 2006, Journal of bacteriology.

[3]  L. Poppe,et al.  The essential tyrosine‐containing loop conformation and the role of the C‐terminal multi‐helix region in eukaryotic phenylalanine ammonia‐lyases , 2006, The FEBS journal.

[4]  A. Gámez,et al.  Phenylalanine ammonia lyase, enzyme substitution therapy for phenylketonuria, where are we now? , 2005, Molecular genetics and metabolism.

[5]  R. Stevens,et al.  Structure-based chemical modification strategy for enzyme replacement treatment of phenylketonuria. , 2005, Molecular genetics and metabolism.

[6]  D. Clarke,et al.  The gene stlA encodes a phenylalanine ammonia-lyase that is involved in the production of a stilbene antibiotic in Photorhabdus luminescens TT01. , 2005, Microbiology.

[7]  G. Schulz,et al.  Phenylalanine ammonia-lyase modified with polyethylene glycol: Potential therapeutic agent for phenylketonuria , 2005, Amino Acids.

[8]  B. Moore,et al.  Biochemical Characterization of a Prokaryotic Phenylalanine Ammonia Lyase , 2005, Journal of bacteriology.

[9]  L. Poppe,et al.  Friedel-Crafts-type mechanism for the enzymatic elimination of ammonia from histidine and phenylalanine. , 2005, Angewandte Chemie.

[10]  R. Stevens,et al.  Development of pegylated forms of recombinant Rhodosporidium toruloides phenylalanine ammonia-lyase for the treatment of classical phenylketonuria. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[11]  R. Croteau,et al.  Cloning, Heterologous Expression, and Characterization of a Phenylalanine Aminomutase Involved in Taxol Biosynthesis* , 2004, Journal of Biological Chemistry.

[12]  G. Schulz,et al.  Structural Basis for the Entrance into the Phenylpropanoid Metabolism Catalyzed by Phenylalanine Ammonia-Lyase , 2004, The Plant Cell Online.

[13]  A. Boodhoo,et al.  Crystal structure of phenylalanine ammonia lyase: multiple helix dipoles implicated in catalysis. , 2004, Biochemistry.

[14]  B. Shen,et al.  A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. , 2003, Journal of the American Chemical Society.

[15]  J. Zoń,et al.  Kinetic analysis of the inhibition of phenylalanine ammonia-lyase by 2-aminoindan-2-phosphonic acid and other phenylalanine analogues. , 2003, Phytochemistry.

[16]  B. Moore,et al.  Inactivation, Complementation, and Heterologous Expression ofencP, a Novel Bacterial Phenylalanine Ammonia-Lyase Gene* , 2002, The Journal of Biological Chemistry.

[17]  L. Poppe,et al.  An active site homology model of phenylalanine ammonia-lyase from Petroselinum crispum. , 2002, European journal of biochemistry.

[18]  J. V. Van Beeumen,et al.  Characterization of a bacterial tyrosine ammonia lyase, a biosynthetic enzyme for the photoactive yellow protein , 2002, FEBS letters.

[19]  G. Schulz,et al.  Autocatalytic peptide cyclization during chain folding of histidine ammonia-lyase. , 2002, Structure.

[20]  R. Dixon,et al.  Dissection of malonyl-coenzyme A decarboxylation from polyketide formation in the reaction mechanism of a plant polyketide synthase. , 2000, Biochemistry.

[21]  G. Schulz,et al.  Crystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile. , 1999, Biochemistry.

[22]  D E McRee,et al.  XtalView/Xfit--A versatile program for manipulating atomic coordinates and electron density. , 1999, Journal of structural biology.

[23]  T. Chang,et al.  A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[25]  A. Vagin,et al.  MOLREP: an Automated Program for Molecular Replacement , 1997 .

[26]  Z. Otwinowski,et al.  Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[27]  D. Jacobs,et al.  Genetic diversity and phylogeny of toxic cyanobacteria determined by DNA polymorphisms within the phycocyanin locus , 1995, Applied and environmental microbiology.

[28]  J. Schmid,et al.  Structural and catalytic properties of the four phenylalanine ammonia-lyase isoenzymes from parsley (Petroselinum crispum Nym.). , 1994, European journal of biochemistry.

[29]  Collaborative Computational,et al.  The CCP4 suite: programs for protein crystallography. , 1994, Acta crystallographica. Section D, Biological crystallography.

[30]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[31]  Wolfgang Kabsch,et al.  Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants , 1993 .

[32]  K. Kalghatgi,et al.  Microbial L-phenylalanine ammonia-lyase. Purification, subunit structure and kinetic properties of the enzyme from Rhizoctonia solani. , 1975, The Biochemical journal.

[33]  L. Vining,et al.  Biosynthesis of cinnamamide and detection of phenylalanine ammonia-lyase in Streptomyces verticillatus. , 1970, Canadian journal of microbiology.

[34]  H. Tabor,et al.  [29] Histidase and urocanase , 1955 .