CN Lyases Catalyzing Addition of Ammonia, Amines, and Amides to CC and CO Bonds

Wu, Bian; Szymański, Wiktor; Crismaru, Ciprian G.; Feringa, Ben L.; Janssen, Dick B.

doi:10.1002/9783527639861.ch18

Cited by 6 publications

(3 citation statements)

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“…Considering this impressive variety of enzyme subclasses, with completely different mechanistic and structural features, a comprehensive report covering all the families mentioned above would be beyond the scope of this review. Several previous accounts and perspectives have already covered in detail the structure and mechanism of specific classes of ammonia-lyases − ,− ,,− and aminomutases. ,, Nevertheless, since great interest has been devoted to some of these families recently for their (potential or demonstrated) synthetic, industrial, or therapeutic applications, the present review intends to cover in detail only these subclasses: aspartate ammonia-lyases (section ), methylaspartate ammonia-lyases (section ), arylalanine ammonia-lyases (section ), and arylalanine aminomutases (section ), with specific emphasis on their applications (sections and ). A few members of these families have been recently demonstrated as valuable tools for the synthesis of high-value-added products (e.g., pharmaceuticals, agrochemicals, chiral building blocks) or for biotherapeutic applications in the treatment of specific diseases.…”

Section: Introductionmentioning

confidence: 99%

Synthetic and Therapeutic Applications of Ammonia-lyases and Aminomutases

et al. 2017

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Ammonia-lyases and aminomutases are mechanistically and structurally diverse enzymes which catalyze the deamination and/or isomerization of amino acids in nature by cleaving or shifting a C-N bond. Of the many protein families in which these enzyme activities are found, only a subset have been employed in the synthesis of optically pure fine chemicals or in medical applications. This review covers the natural diversity of these enzymes, highlighting particular enzyme classes that are used within industrial and medical biotechnology. These highlights detail the discovery and mechanistic investigations of these commercially relevant enzymes, along with comparisons of their various applications as stand-alone catalysts, components of artificial biosynthetic pathways and biocatalytic or chemoenzymatic cascades, and therapeutic tools for the potential treatment of various pathologies.

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Section: Introductionmentioning

confidence: 99%

Synthetic and Therapeutic Applications of Ammonia-lyases and Aminomutases

et al. 2017

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“…Application of ATs in biocatalysis has mainly been investigated for the production of proteinogenic amino acids, unnatural amino acids, and various other amines and amino alcohols (28)(29)(30)(31)(32)(33)(34). The catalytic activities can be quite high (apparent k cat values up to 50 s Ϫ1 ) (35), and apart from PLP, which is sometimes added, there is no requirement for an external cofactor.…”

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confidence: 99%

Biochemical Properties and Crystal Structure of a β-Phenylalanine Aminotransferase from Variovorax paradoxus

Crismaru

Wybenga

Szymański

et al. 2013

Appl Environ Microbiol

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e By selective enrichment, we isolated a bacterium that can use ␤-phenylalanine as a sole nitrogen source. It was identified by 16S rRNA gene sequencing as a strain of Variovorax paradoxus. Enzyme assays revealed an aminotransferase activity. Partial genome sequencing and screening of a cosmid DNA library resulted in the identification of a 1,302-bp aminotransferase gene, which encodes a 46,416-Da protein. The gene was cloned and overexpressed in Escherichia coli. The recombinant enzyme was purified and showed a specific activity of 17.5 U mg ؊1 for (S)-␤-phenylalanine at 30°C and 33 U mg ؊1 at the optimum temperature of 55°C. The ␤-specific aminotransferase exhibits a broad substrate range, accepting ortho-, meta-, and para-substituted ␤-phenylalanine derivatives as amino donors and 2-oxoglutarate and pyruvate as amino acceptors. The enzyme is highly enantioselective toward (S)-␤-phenylalanine (enantioselectivity [E], >100) and derivatives thereof with different substituents on the phenyl ring, allowing the kinetic resolution of various racemic ␤-amino acids to yield (R)-␤-amino acids with >95% enantiomeric excess (ee). The crystal structures of the holoenzyme and of the enzyme in complex with the inhibitor 2-aminooxyacetate revealed structural similarity to the ␤-phenylalanine aminotransferase from Mesorhizobium sp. strain LUK. The crystal structure was used to rationalize the stereo-and regioselectivity of V. paradoxus aminotransferase and to define a sequence motif with which new aromatic ␤-amino acid-converting aminotransferases may be identified.

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“…As a common strategic working line for IP construction, several industries have focused on the (successful) protection of novel sequences of lyases (establishing several degrees of homology), which can be subsequently used for biocatalytic purposes. As relevant examples, Codexis was granted patents ( [314], granted in 2019) that comprise examples of phenylammonia lyase variants (PAL, a C-N lyase [315]) with improved tolerance to pH, higher activity, or resistance to enzymatic proteolysis (key amino acidic residues of the sequence are given). In a similar approach, another patent granted in 2019 [316] protect novel another C-N lyase, tyrosine ammonia lyase variants (TAL), with analogous focus on improved activities, and including thermostability as well.…”

Section: Granted Patents Related To Lyases In Asymmetric Synthesismentioning

confidence: 99%

Biocatalysis as Useful Tool in Asymmetric Synthesis: An Assessment of Recently Granted Patents (2014–2019)

Marı́a¹,

Gonzalo

Alcántara

2019

Catalysts

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The broad interdisciplinary nature of biocatalysis fosters innovation, as different technical fields are interconnected and synergized. A way to depict that innovation is by conducting a survey on patent activities. This paper analyses the intellectual property activities of the last five years (2014–2019) with a specific focus on biocatalysis applied to asymmetric synthesis. Furthermore, to reflect the inventive and innovative steps, only patents that were granted during that period are considered. Patent searches using several keywords (e.g., enzyme names) have been conducted by using several patent engine servers (e.g., Espacenet, SciFinder, Google Patents), with focus on granted patents during the period 2014–2019. Around 200 granted patents have been identified, covering all enzyme types. The inventive pattern focuses on the protection of novel protein sequences, as well as on new substrates. In some other cases, combined processes, multi-step enzymatic reactions, as well as process conditions are the innovative basis. Both industries and academic groups are active in patenting. As a conclusion of this survey, we can assert that biocatalysis is increasingly recognized as a useful tool for asymmetric synthesis and being considered as an innovative option to build IP and protect synthetic routes.

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CN Lyases Catalyzing Addition of Ammonia, Amines, and Amides to CC and CO Bonds

Cited by 6 publications

References 104 publications

Synthetic and Therapeutic Applications of Ammonia-lyases and Aminomutases

Synthetic and Therapeutic Applications of Ammonia-lyases and Aminomutases

Biochemical Properties and Crystal Structure of a β-Phenylalanine Aminotransferase from Variovorax paradoxus

Biocatalysis as Useful Tool in Asymmetric Synthesis: An Assessment of Recently Granted Patents (2014–2019)

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