Enzymes with noncanonical amino acids

Zhao, Jingming; Burke, Ashleigh J.; Green, Anthony P.

doi:10.1016/j.cbpa.2020.01.006

Cited by 48 publications

(42 citation statements)

References 61 publications

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“…Enzymes from biosynthetic pathways to NcAAs ( Hedges and Ryan, 2020 ) are clear candidates for MECs expansion. On the other hand, information of specific enzymes for functionalization of AAs or AA transformation into other important pharmaceutical compounds is also accumulating in the literature (e.g., Smirnov et al, 2012 ; Busto et al, 2014 ; Hönig et al, 2017 ; Hyslop et al, 2018 ; Parthasarathy et al, 2018 ; Peters and Buller, 2019 ; McDonald et al, 2019 ; Hedges and Ryan, 2020 ; Mindt et al, 2020 ; Song et al, 2020 ; Wendisch, 2020 ; Zhang et al, 2020 ; Zhao et al, 2020 ). These enzymes are, in principle, complementary to well stablished NcAA-production MECs.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic engineering methodologies allow gene libraries of 10 1 -10 8 variants and thus, random incorporation of NcAAs in their sequence; sampling can thus be carried out by high throughput approaches, greatly shortening the time needed for new antimicrobial development (Baumann et al, 2017). Among them, the possibility to engineer proteins to incorporate site-specifically different NcAAs has had a major impact the development of this field (Agostini et al, 2017;Zhao et al, 2020). This technology has removed the constraints imposed by nature on the use of the 22-genetically encoded AAs, allowing to insert new properties and/or improved functionalities on protein scaffolds.…”

Section: Biomedical and Biotechnological Applications Of Ncaasmentioning

confidence: 99%

“…Some examples are improvements in enzyme catalytic efficiency, chemical and/or thermal stability, substrate scope, enantio- and stereoselectivity or inhibition. Also, bioorthogonal functionalization, spectroscopic probes, photo-cross-linking, metal-chelating or post-translational modification-mimicking has been reported ( Agostini et al, 2017 ; Almhjell and Mills, 2018 ; Rezhdo et al, 2019 ; Zhao et al, 2020 ). Thus, the huge advances on the standardization of methodologies for the production of enzymes incorportating NcAAs ( Smolskaya and Andreev, 2019 ; Hammerling et al, 2020 ) are also boosting the application and economic significance of NcAAs.…”

Section: Introductionmentioning

confidence: 99%

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Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Martínez‐Rodríguez

Torres

Sánchez

et al. 2020

Front. Bioeng. Biotechnol.

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The 22 genetically encoded amino acids (AAs) present in proteins (the 20 standard AAs together with selenocysteine and pyrrolysine), are commonly referred as proteinogenic AAs in the literature due to their appearance in ribosome-synthetized polypeptides. Beyond the borders of this key set of compounds, the rest of AAs are generally named imprecisely as non-proteinogenic AAs, even when they can also appear in polypeptide chains as a result of post-transductional machinery. Besides their importance as metabolites in life, many of D-α-and L-α-"non-canonical" amino acids (NcAAs) are of interest in the biotechnological and biomedical fields. They have found numerous applications in the discovery of new medicines and antibiotics, drug synthesis, cosmetic, and nutritional compounds, or in the improvement of protein and peptide pharmaceuticals. In addition to the numerous studies dealing with the asymmetric synthesis of NcAAs, many different enzymatic pathways have been reported in the literature allowing for the biosynthesis of NcAAs. Due to the huge heterogeneity of this group of molecules, this review is devoted to provide an overview on different established multienzymatic cascades for the production of non-canonical D-α-and L-α-AAs, supplying neophyte and experienced professionals in this field with different illustrative examples in the literature. Whereas the discovery of new or newly designed enzymes is of great interest, dusting off previous enzymatic methodologies by a "back and to the future" strategy might accelerate the implementation of new or improved multienzymatic cascades.

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Section: Discussionmentioning

confidence: 99%

Section: Biomedical and Biotechnological Applications Of Ncaasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Martínez‐Rodríguez

Torres

Sánchez

et al. 2020

Front. Bioeng. Biotechnol.

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“…[7][8][9] By engineering components of the translation machinery, proteins containing novel functionality can now be biosynthesized both in vitro and in vivo. This technology has made it possible to investigate structure-function relationships, [10] probe receptor-ligand interactions, [11][12][13] study the inactivation mechanism of ion channels, [14] create and evolve novel enzymes, [15][16][17] and tailor protein therapeutic agents, [18] among other applications.…”

Section: Introductionmentioning

confidence: 99%

Trapping Transient Protein Species by Genetic Code Expansion

Tinzl

Hilvert

2020

ChemBioChem

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Nature employs a limited number of genetically encoded amino acids for the construction of functional proteins. By engineering components of the cellular translation machinery, however, it is now possible to genetically encode noncanonical building blocks with tailored electronic and structural properties. The ability to incorporate unique chemical functionality into proteins provides a powerful tool to probe mechanism and create novel function. In this minireview, we highlight several recent studies that illustrate how noncanonical amino acids have been used to capture and characterize reactive intermediates, fine-tune the catalytic properties of enzymes, and stabilize short-lived protein-protein complexes.

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“…As is well known, 20 natural amino acids are the main building blocks of proteins, the macromolecules that perform a broad spectrum of functions within organisms (Qin et al, 2015). Unnatural amino acids (UAAs) also called noncanonical amino acids are analogs or metabolic intermediates of the 20 natural amino acids with only minor structural differences-often just a chemical functional group-which is beneficial for analyzing their effects on enzyme functions (Zhao et al, 2020). Since UAAs are of high chemical diversity, possess strong site specificity, and introduce little disturbance to the protein structure, it is widely applied in protein engineering, virus vaccine development, and medical therapeutics (Minnihan et al, 2011;Si et al, 2016;Young and Schultz, 2018).…”

Section: Introductionmentioning

confidence: 99%

Development and Testing of Force Field Parameters for Phenylalanine and Tyrosine Derivatives

Wang

2020

Front. Mol. Biosci.

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Theoretical analyses are valuable for the exploration of the effects of unnatural amino acids on enzyme functions; however, many necessary parameters for unnatural amino acids remain lacking. In this study, we developed and tested force field parameters compatible with Amber ff14SB for 18 phenylalanine and tyrosine derivatives. The charge parameters were derived from ab initio calculations using the RESP fitting approach and then adjusted to reproduce the benchmark relative energies (at the MP2/TZ level) of the α- and β-backbones for each unnatural amino acid dipeptide. The structures optimized under the proposed force field parameters for the 18 unnatural amino acid dipeptides in both the α- and β-backbone forms were in good agreement with their QM structures, as the average RMSD was as small as 0.1 Å. The force field parameters were then tested in their application to seven proteins containing unnatural amino acids. The RMSDs of the simulated configurations of these unnatural amino acids were approximately 1.0 Å compared with those of the crystal structures. The vital interactions between proteins and unnatural amino acids in five protein–ligand complexes were also predicted using MM/PBSA analysis, and they were largely consistent with experimental observations. This work will provide theoretical aid for drug design involving unnatural amino acids.

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Enzymes with noncanonical amino acids

Cited by 48 publications

References 61 publications

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Trapping Transient Protein Species by Genetic Code Expansion

Development and Testing of Force Field Parameters for Phenylalanine and Tyrosine Derivatives

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