Thermal Bifunctionality of Bacterial Phenylalanine Aminomutase and Ammonia Lyase Enzymes

Chesters, Christopher; Wilding, M. A.; Goodall, Mark; Micklefield, Jason

doi:10.1002/anie.201200669

Cited by 35 publications

(47 citation statements)

References 33 publications

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“…The tentative higher thermostability of bacterial PALs was also supported by investigations of the enzyme coded by EncP gene of the thermotolerant marine bacterium Streptomyces maritimus. This protein was shown to function as a PAL at 30°C [48], [54] and its PAL activity increased exponentially from 30 to 64°C, reaching a maximum activity at 74°C [54]. The enzyme encoded by the gene AdmH of the mesophilic bacterium Pantoea agglomerans is a phenylalanine 2,3-aminomutase ( Pa PAM) which provides ( S )-β-phenylalanine required for the biosynthesis of the antibiotic andrimid [56], [57].…”

Section: Introductionmentioning

confidence: 99%

“…The enzyme encoded by the gene AdmH of the mesophilic bacterium Pantoea agglomerans is a phenylalanine 2,3-aminomutase ( Pa PAM) which provides ( S )-β-phenylalanine required for the biosynthesis of the antibiotic andrimid [56], [57]. Unexpectedly, at elevated temperature enzyme AdmH exhibited thermophilic PAL activity similar to EncP [54].…”

Section: Introductionmentioning

confidence: 99%

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Expression and Properties of the Highly Alkalophilic Phenylalanine Ammonia-Lyase of Thermophilic Rubrobacter xylanophilus

et al. 2014

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The sequence of a phenylalanine ammonia-lyase (PAL; EC: 4.3.1.24) of the thermophilic and radiotolerant bacterium Rubrobacter xylanophilus (RxPAL) was identified by screening the genomes of bacteria for members of the phenylalanine ammonia-lyase family. A synthetic gene encoding the RxPAL protein was cloned and overexpressed in Escherichia coli TOP 10 in a soluble form with an N-terminal His6-tag and the recombinant RxPAL protein was purified by Ni-NTA affinity chromatography. The activity assay of RxPAL with l-phenylalanine at various pH values exhibited a local maximum at pH 8.5 and a global maximum at pH 11.5. Circular dichroism (CD) studies showed that RxPAL is associated with an extensive α-helical character (far UV CD) and two distinctive near-UV CD peaks. These structural characteristics were well preserved up to pH 11.0. The extremely high pH optimum of RxPAL can be rationalized by a three-dimensional homology model indicating possible disulfide bridges, extensive salt-bridge formation and an excess of negative electrostatic potential on the surface. Due to these properties, RxPAL may be a candidate as biocatalyst in synthetic biotransformations leading to unnatural l- or d-amino acids or as therapeutic enzyme in treatment of phenylketonuria or leukemia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression and Properties of the Highly Alkalophilic Phenylalanine Ammonia-Lyase of Thermophilic Rubrobacter xylanophilus

et al. 2014

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“…Current members, whose activity has been unambiguously confirmed experimentally, include (i) two PAMs, PaPAM from Pantoea agglomerans that yields (S)-β-phenylalanine (13)(14)(15)(16) and TcPAM from Taxus canadensis that yields (R)-β-phenylalanine (17,18), and (ii) five TAMs of SgcC4 from S. globisporus (6, 7), MdpC4 from Actinomadura madurae (19), MfTAM from Myxococcus fulvus (20), and MxTAM from Myxococcus sp. Mx-BO (20), all of which afford (S)-β-tyrosine, and CmdF from Chondromyces crocatus that yields (R)-β-tyrosine (21).…”

Section: Streptomyces Globisporusmentioning

confidence: 99%

“…Mechanistic and structural characterizations of the MIO-containing aminomutases as a family have unveiled much unique chemistry, enzymology, and structural biology (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and exploitation of these enzymes as biocatalysts has provided access to α-and β-amino acids, which are difficult to prepare by other means (4,37). However, ʟ-phenylalanine and ʟ-tyrosine remain the only two known natural substrates (3)(4)(5).…”

Section: ·Smentioning

confidence: 99%

A new member of the 4-methylideneimidazole-5-one–containing aminomutase family from the enediyne kedarcidin biosynthetic pathway

Huang¹,

Lohman²,

Huang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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4-Methylideneimidazole-5-one (MIO)-containing aminomutases catalyze the conversion of l -α-amino acids to β-amino acids with either an ( R ) or an ( S ) configuration. l -Phenylalanine and l -tyrosine are the only two natural substrates identified to date. The enediyne chromophore of the chromoprotein antitumor antibiotic kedarcidin (KED) harbors an ( R )-2-aza-3-chloro-β-tyrosine moiety reminiscent of the ( S )-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, the biosynthesis of which uncovered the first known MIO-containing aminomutase, SgcC4. Comparative analysis of the KED and C-1027 biosynthetic gene clusters inspired the proposal for ( R )-2-aza-3-chloro-β-tyrosine biosynthesis starting from 2-aza- l -tyrosine, featuring KedY4 as a putative MIO-containing aminomutase. Here we report the biochemical characterization of KedY4, confirming its proposed role in KED biosynthesis. KedY4 is an MIO-containing aminomutase that stereospecifically catalyzes the conversion of 2-aza- l -tyrosine to ( R )-2-aza-β-tyrosine, exhibiting no detectable activity toward 2-aza- l -phenylalanine or l -tyrosine as an alternative substrate. In contrast, SgcC4, which stereospecifically catalyzes the conversion of l -tyrosine to ( S )-β-tyrosine in C-1027 biosynthesis, exhibits minimal activity with 2-aza- l -tyrosine as an alternative substrate but generating ( S )-2-aza-β-tyrosine, a product with the opposite stereochemistry of KedY4. This report of KedY4 broadens the scope of known substrates for the MIO-containing aminomutase family, and comparative studies of KedY4 and SgcC4 provide an outstanding opportunity to examine how MIO-containing aminomutases control substrate specificity and product enantioselectivity.

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“…In microorganisms, PAL was demonstrated for the first time by Ogata et al (1966). Subsequently, PAL has been found in other fungi (D'Cunha et al, 1996a;Fiske & Kane, 1984;Gilbert & Tully, 1982;Gilbert et al, 1983;Marusich et al, 1981;Wick & Willis, 1982) and a few bacteria (Berner et al, 2006;Chesters et al, 2012;Kyndt et al, 2002;Williams et al, 2005;Xiang & Moore, 2005;Zhu et al, 2012). Although there is no direct evidence for the significance of this enzyme except as a catabolic function in microorganisms, in yeast this enzyme appears to serve a catabolic function.…”

Section: Introductionmentioning

confidence: 99%

Biotechnological production and applications of microbial phenylalanine ammonia lyase: a recent review

Cui

Qiu

Fan

et al. 2013

Critical Reviews in Biotechnology

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Phenylalanine ammonia lyase (PAL) catalyzes the nonoxidative deamination of l-phenylalanine to form trans-cinnamic acid and a free ammonium ion. It plays a major role in the catabolism of l-phenylalanine. The presence of PAL has been reported in diverse plants, some fungi, Streptomyces and few Cyanobacteria. In the past two decades, PAL has gained considerable significance in several clinical, industrial and biotechnological applications. Since its discovery, much knowledge has been gathered with reference to the enzyme's importance in phenyl propanoid pathway of plants. In contrast, there is little knowledge about microbial PAL. Furthermore, the commercial source of the enzyme has been mainly obtained from the fungi. This study focuses on the recent advances on the physiological role of microbial PAL and the improvements of PAL biotechnological production both from our laboratory and many others as well as the latest advances on the new applications of microbial PAL.

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Thermal Bifunctionality of Bacterial Phenylalanine Aminomutase and Ammonia Lyase Enzymes

Cited by 35 publications

References 33 publications

Expression and Properties of the Highly Alkalophilic Phenylalanine Ammonia-Lyase of Thermophilic Rubrobacter xylanophilus

Expression and Properties of the Highly Alkalophilic Phenylalanine Ammonia-Lyase of Thermophilic Rubrobacter xylanophilus

A new member of the 4-methylideneimidazole-5-one–containing aminomutase family from the enediyne kedarcidin biosynthetic pathway

Biotechnological production and applications of microbial phenylalanine ammonia lyase: a recent review

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