Research Topic

PLP-Dependent Enzymes: Extraordinary Versatile Catalysts and Ideal Biotechnological Tools for the Production of Unnatural Amino Acids and Related Compounds

About this Research Topic

Amino acids and amines are among the most important molecules in nature and chemistry. They play central roles both as intermediates in metabolism and as building blocks of proteins and pharmaceuticals. By incorporating an alternative amino acids into proteins, the available chemical options to achieve ...

Amino acids and amines are among the most important molecules in nature and chemistry. They play central roles both as intermediates in metabolism and as building blocks of proteins and pharmaceuticals. By incorporating an alternative amino acids into proteins, the available chemical options to achieve additional functionalities is substantially enlarged. For example, hydroxy amino acids can be site-specifically installed into proteins to define specific sites for chemical hydrolysis. In addition, unnatural amino acids can be used to derivatise proteins with PEG molecules, sugars, oligonucleotides, fluorophores, peptides, and other unique synthetic moieties. Special unnatural amino acids, e.g. fluorinated analogues or sterically hindered α-tetrasubstituted α-amino acids, have highly attractive unique features in drug discovery and development, as chiral blocks during organic synthesis of active pharmaceutical ingredients, as well as in disease diagnostics as potential biomarkers.

The biocatalytic asymmetric synthesis of unnatural amino acids raised great attention in recent years. In living organisms enzymes that use pyridoxal-5’-phosphate (PLP) cofactor catalyse a wide variety of biochemical reactions involving amino acids substrates and their analogues. These enzymes catalyse a number of diverse chemicals reactions, such as decarboxylation, transamination, racemization, β- and γ-elimination, carbon-carbon bond cleavage and formation. Due to their catalytic versatility, PLP-enzymes attracted interest as powerful tool in biotechnology, to be exploited in the semi-synthetic production of natural amino acids, and most recently, unnatural amino acids and their related compounds. Further, engineering of metabolic pathways mediated by PLP-dependent enzymes is a promising approach to provide cells with unnatural amino acids, produced intracellularly from simple carbon sources or precursors.

So far, the described protocols for the asymmetric synthesis of unnatural amino acids using PLP-enzymes include application of threonine aldolases for the synthesis of L- and D-β-hydroxy amino acids, kynureninase, tryptophanase and tryptophan synthase for the synthesis of aromatic amino acids, O-acetyl(homo)serine sulfhydrylase for the synthesis of (homo)cysteine derivatives, and a wealth of protocols describing stereoselective synthesis of amino acids and amines using PLP-dependent transaminases. However, still many PLP-dependent enzymes were poorly investigated as potential catalysts for the synthesis of unnatural amino acids. Of particular interest in this context are PLP-dependent enzymes from extremophile organisms.

This Research topic will focus on new approaches for the synthesis of unnatural amino acids and their analogues with the help of PLP-dependent enzymes. Moreover, the techniques to alter the reaction and substrate specificity of PLP-dependent enzymes, as well as new knowledge on the structure-function relationship in this class of enzymes will be included. Investigations on the intrinsic catalytic promiscuity of PLP cofactor to develop new catalytic functions in the scaffold of PLP-dependent enzymes will also be considered.

This Research Topic is intended to become an international platform for researchers to summarise the most recent developments and ideas in the field of PLP-dependent enzymes, with special emphasis on their application in biotechnology and biocatalysis.


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Submission Deadlines

28 September 2018 Manuscript
31 March 2019 Manuscript Extension

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

28 September 2018 Manuscript
31 March 2019 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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