Amides in Nature and Biocatalysis

Pitzer, Julia; Steiner, Kerstin

doi:10.1016/j.jbiotec.2016.03.023

Cited by 99 publications

(59 citation statements)

References 149 publications

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“…[11][12][13] Thet hree-domain topology of the enzyme suggests that, in the presence of ATPb ut the absence of NADPH, the substrate carboxylic acid might still be activated, yielding the acyl adenylate or thioester.B oth intermediates could potentially react with an external nucleophile,such as an amine,to generate amides ( Figure 1). Amidation would be of particular interest because many natural amide synthetases,s uch as NRPS [14] and ATP-grasp enzymes [15,16] ,s uffer from very narrow substrate specificity,w hich limits their applications in biocatalysis.A lternatively,h ydrolases (such as lipases [17] and proteases [18] ), which are commonly used for amide formation, [2] require systems in which very little water is present, such as organic solvents,todrive the reaction towards amide bond formation. [19][20][21][22] Four CARc andidates (CARmm from Mycobacterium marinum, [3] CARni from Nocardia iowensis, [4] CARtp from Tsukamurella paurometabola, [10] and CARse from Segniliparus rotundus, [23] )were produced recombinantly in Escherichia coli,w ith the coexpressed gene for the Bacillus subtilis phosphopantetheinyl transferase (PPTase;S fp), [24] which is required for post-translational addition of the PPant group.…”

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confidence: 99%

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

et al. 2017

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Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids to aldehydes using the cofactors adenosine triphosphate and nicotinamide adenine dinucleotide phosphate, and have become attractive biocatalysts for organic synthesis. Mechanistic understanding of CARs was used to expand reaction scope, generating biocatalysts for amide bond formation from carboxylic acid and amine. CARs demonstrated amidation activity for various acids and amines. Optimization of reaction conditions, with respect to pH and temperature, allowed for the synthesis of the anticonvulsant ilepcimide with up to 96 % conversion. Mechanistic studies using site-directed mutagenesis suggest that, following initial enzymatic adenylation of substrates, amidation of the carboxylic acid proceeds by direct reaction of the acyl adenylate with amine nucleophiles.

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confidence: 99%

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

et al. 2017

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“…Both intermediates could potentially react with an external nucleophile, such as an amine, to generate amides (Figure ). Amidation would be of particular interest because many natural amide synthetases, such as NRPS and ATP‐grasp enzymes, suffer from very narrow substrate specificity, which limits their applications in biocatalysis. Alternatively, hydrolases (such as lipases and proteases), which are commonly used for amide formation, require systems in which very little water is present, such as organic solvents, to drive the reaction towards amide bond formation …”

Section: Figurementioning

confidence: 99%

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

et al. 2017

View full text Add to dashboard Cite

Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids to aldehydes using the cofactors adenosine triphosphate and nicotinamide adenine dinucleotide phosphate, and have become attractive biocatalysts for organic synthesis. Mechanistic understanding of CARs was used to expand reaction scope, generating biocatalysts for amide bond formation from carboxylic acid and amine. CARs demonstrated amidation activity for various acids and amines. Optimization of reaction conditions, with respect to pH and temperature, allowed for the synthesis of the anticonvulsant ilepcimide with up to 96 % conversion. Mechanistic studies using site‐directed mutagenesis suggest that, following initial enzymatic adenylation of substrates, amidation of the carboxylic acid proceeds by direct reaction of the acyl adenylate with amine nucleophiles.

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“…Despite the information abundance on the amide functionality, [1][2][3] there is a continued interest in chemical synthesis, [4][5][6][7][8][9] biosynthesis [10][11][12] and reactivity [13][14][15][16][17][18][19] of amides due to their importance in medicine, biology, chemistry and other related interdisciplinary sciences. [20][21][22][23][24][25][26][27][28][29][30][31][32] This relevance encourages the research of the amide group's fundamental characteristics, e. g. the cis-trans isomerization barrier, [33][34][35][36] the resonance energy [37][38][39] or acid-base properties.…”

Section: Introductionmentioning

confidence: 99%

How Strong is Hydrogen Bonding to Amide Nitrogen?

et al. 2020

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The protonation of the carboxamide nitrogen atom is an essential part of in vivo and in vitro processes (cis‐trans isomerization, amides hydrolysis etc). This phenomenon is well studied in geometrically strongly distorted amides, although there is little data concerning the protonation of undistorted amides. In the latter case, the participation of amide nitrogen in hydrogen bonding (which can be regarded as the incipient state of a proton transfer process) is less well‐studied. Thus, it would be a worthy goal to investigate the enthalpy of this interaction. We prepared and investigated a set of peri‐substituted naphthalenes containing the protonated dimethylamino group next to the amide nitrogen atom (“amide proton sponges”), which could serve as models for the study of an intramolecular hydrogen bond with the amide nitrogen atom. X‐Ray analysis, NMR spectra, basicity values as well as quantum chemical calculations revealed the existence of a hydrogen bond with the amide nitrogen, that should be attributed to the borderline between moderate and weak intramolecular hydrogen bonds (2–7 kcal ⋅ mol−1).

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Amides in Nature and Biocatalysis

Cited by 99 publications

References 149 publications

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

How Strong is Hydrogen Bonding to Amide Nitrogen?

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