Chemical modification of enzymes to improve biocatalytic performance

Giri, Pritam; Pagar, Amol D.; Patil, Mahesh D.; Yun, Hyungdon

doi:10.1016/j.biotechadv.2021.107868

Cited by 51 publications

(26 citation statements)

References 261 publications

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“…The chemical modification and ncAA incorporation methods have emerged as an important alternative to the traditional enzyme engineering approaches like directed evolution and rational design ( Giri et al, 2021 ; Pagar et al, 2021 ). These methods used independently or together have dramatically expanded the chemical diversity for proteins, which has provided protein engineers with powerful tools for enzymes engineering ( Pagar et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Over the last 2 decades, more than 200 ncAAs have been genetically encoded in prokaryotes and eukaryotes ( Pagar et al, 2021 ). Apart from peptide modification, antibody development for pharmaceutical use, ncAAs has been widely applied in enzyme engineering research to illustrate the enzyme mechanisms, enhance enzyme activity, and even generate new catalytic mechanisms into protein scaffolds ( Agostini et al, 2017 ; Won et al, 2019b ; Drienovská and Roelfes, 2020 ; Giri et al, 2021 ; Pagar et al, 2021 ). The examples include ncAAs with metal chelating, photo-crosslinking, extended disulfide forming, orthogonal reactive, and unique pi-pi interaction properties ( Pagar et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Non-Canonical Amino Acid-Based Engineering of (R)-Amine Transaminase

et al. 2022

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Non-canonical amino acids (ncAAs) have been utilized as an invaluable tool for modulating the active site of the enzymes, probing the complex enzyme mechanisms, improving catalytic activity, and designing new to nature enzymes. Here, we report site-specific incorporation of p-benzoyl phenylalanine (pBpA) to engineer (R)-amine transaminase previously created from d-amino acid aminotransferase scaffold. Replacement of the single Phe88 residue at the active site with pBpA exhibits a significant 15-fold and 8-fold enhancement in activity for 1-phenylpropan-1-amine and benzaldehyde, respectively. Reshaping of the enzyme’s active site afforded an another variant F86A/F88pBpA, with 30% higher thermostability at 55°C without affecting parent enzyme activity. Moreover, various racemic amines were successfully resolved by transaminase variants into (S)-amines with excellent conversions (∼50%) and enantiomeric excess (>99%) using pyruvate as an amino acceptor. Additionally, kinetic resolution of the 1-phenylpropan-1-amine was performed using benzaldehyde as an amino acceptor, which is cheaper than pyruvate. Our results highlight the utility of ncAAs for designing enzymes with enhanced functionality beyond the limit of 20 canonical amino acids.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Non-Canonical Amino Acid-Based Engineering of (R)-Amine Transaminase

et al. 2022

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“…Kinetic productivity analysis can be employed to assess the catalytic capacity of genetically and chemically modified variants [3,4], whole cells [5], the effect of immobilization carriers on productivity [6], difference between isoforms isolated from a range of organisms or tissues, and the effect of reaction solution additives [7]. a The Web of Science Core Collection was used for the search, and the analysis date range was 2000-2021.…”

Section: Introductionmentioning

confidence: 99%

Evaluating Enzymatic Productivity—The Missing Link to Enzyme Utility

Siddiqui

Ertan

Poljak

et al. 2022

IJMS

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Kinetic productivity analysis is critical to the characterization of enzyme catalytic performance and capacity. However, productivity analysis has been largely overlooked in the published literature. Less than 0.01% of studies which report on enzyme characterization present productivity analysis, despite the fact that this is the only measurement method that provides a reliable indicator of potential commercial utility. Here, we argue that reporting productivity data involving native, modified, and immobilized enzymes under different reaction conditions will be of immense value in optimizing enzymatic processes, with a view to accelerating biotechnological applications. With the use of examples from wide-ranging studies, we demonstrate that productivity is a measure of critical importance to the translational and commercial use of enzymes and processes that employ them. We conclude the review by suggesting steps to maximize the productivity of enzyme catalyzed reactions.

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“…Enzymes are interesting catalysts, which provide highly sustainable alternatives to conventional chemical methods, − arising in the last years as efficient catalysts for synthesis under mild reaction conditions for a great scope of reactions, with high selectivity and large substrate specificity. − Hydrolases constitute a class of enzymes, which catalyze either hydrolytic or reverse bond-formation reactions. Due to their easy handling to not needing a cofactor and their ability to perform in aqueous systems and in organic solvents, hydrolases have been incorporated into numerous synthetic routes, allowing the efficient production of alcohols, amines, esters, amides, epoxides, and nitriles, among other relevant molecules. − This class of enzymes has been also industrially applied to the synthesis of, for example, pharmaceuticals, agrochemicals, and several high added-value substances. ,, …”

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confidence: 99%

“…In the last years, lipases have been extensively used in nonaqueous media for a variety of organic transformations such as aminolysis, esterifications, polymerizations, etc. ,,− Using lipases, we have obtained diverse biologically active novel compounds from multiple substrates, with applications as potential antiparasitic, ,, antitumoral, and antiviral agents. , …”

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confidence: 99%

Lipase-Catalyzed Synthesis and Biological Evaluation of N-Picolineamides as Trypanosoma cruzi Antiproliferative Agents

García

Musikant

Escalona

et al. 2023

ACS Med. Chem. Lett.

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In our search for new safe antiparasitic agents, an enzymatic pathway was applied to synthesize a series of N-pyridinylmethyl amides derived from structurally different carboxylic acids. Thirty derivatives, including 11 new compounds, were prepared through lipase-catalyzed acylation in excellent yields. In order to optimize the synthetic methodology, the impact of different reaction parameters was analyzed. Some compounds were evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for American trypanosomiasis (Chagas’ disease). Some of them showed significant activity as parasite proliferation inhibitors. Amides derived from 2-aminopicoline and stearic and elaidic acids were as potent as nifurtimox against the amastigote form of T. cruzi, the clinically relevant form of the parasite. Even more, a powerful synergism between nifurtimox and N-(pyridin-2-ylmethyl)stereamide was observed, almost completely inhibiting the proliferation of the parasite. Besides, the obtained compounds showed no toxicity in Vero cells, making them excellent potential candidates as lead drugs.

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Chemical modification of enzymes to improve biocatalytic performance

Cited by 51 publications

References 261 publications

Non-Canonical Amino Acid-Based Engineering of (R)-Amine Transaminase

Non-Canonical Amino Acid-Based Engineering of (R)-Amine Transaminase

Evaluating Enzymatic Productivity—The Missing Link to Enzyme Utility

Lipase-Catalyzed Synthesis and Biological Evaluation of N-Picolineamides as Trypanosoma cruzi Antiproliferative Agents

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