Biocatalytic Friedel–Crafts Acylation and Fries Reaction

Schmidt, Nina G.; Pavkov‐Keller, Tea; Richter, Nina; Wiltschi, Birgit; Gruber, Karl; Kroutil, Wolfgang

doi:10.1002/anie.201703270

Cited by 58 publications

(83 citation statements)

References 37 publications

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“…It was shown that Pp ATase accepts various C‐ or O‐acyl donors such as isopropenyl acetate and transfers an acetyl moiety to a phenolic acceptor in a Friedel–Crafts‐type acetylation . The enzyme complex also shows chemical reaction promiscuity and accepts aniline derivatives as substrates for amide formation …”

Section: Introductionmentioning

confidence: 99%

Structure and Catalytic Mechanism of a Bacterial Friedel–Crafts Acylase

et al. 2018

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C−C bond‐forming reactions are key transformations for setting up the carbon frameworks of organic compounds. In this context, Friedel–Crafts acylation is commonly used for the synthesis of aryl ketones, which are common motifs in many fine chemicals and natural products. A bacterial multicomponent acyltransferase from Pseudomonas protegens ( Pp ATase) catalyzes such Friedel–Crafts C‐acylation of phenolic substrates in aqueous solution, reaching up to >99 % conversion without the need for CoA‐activated reagents. We determined X‐ray crystal structures of the native and ligand‐bound complexes. This multimeric enzyme consists of three subunits: PhlA, PhlB, and PhlC, arranged in a Phl(A 2 C 2 ) 2 B 4 composition. The structure of a reaction intermediate obtained from crystals soaked with the natural substrate 1‐(2,4,6‐trihydroxyphenyl)ethanone together with site‐directed mutagenesis studies revealed that only residues from the PhlC subunits are involved in the acyl transfer reaction, with Cys88 very likely playing a significant role during catalysis. These structural and mechanistic insights form the basis of further enzyme engineering efforts directed towards enhancing the substrate scope of this enzyme.

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Section: Introductionmentioning

confidence: 99%

Structure and Catalytic Mechanism of a Bacterial Friedel–Crafts Acylase

et al. 2018

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“…6), since we were interested to apply this enzyme for various acyl donors and acceptors (Schmidt et al 2017). Thus, the ATase activity in the following studies was evaluated based on the formation of the C-acetyl product 9 arising from the bioacetylation of model substrate 8 by DAPG.…”

Section: Resultsmentioning

confidence: 99%

“…HCl (3.6 vol%), trans -cinnamaldehyde (3.6 vol%)]. Shake flask cultivation, expression of the wild-type, and recombinant ATase was performed as described previously (Schmidt et al 2017). …”

Section: Methodsmentioning

confidence: 99%

“…2) into one molecule of PG ( 7 ) and DAPG ( 5 ) in the forward reaction (Hayashi et al 2012; Yang and Cao 2012; Almario et al 2017). Our previous report proved that a multi-component ATase from Pseudomonas protegens catalyzes transfer of acyl moieties, not only from natural but also from non-natural donor substrates, to the aromatic ring of a phenolic acceptor substrate by forming a new C-C bond in a Friedel-Crafts-type acylation reaction (Schmidt et al 2017). In this work, we report on the cloning of the key biosynthetic operon phlACB , into a bacterial expression vector to produce the ATase in E. coli and developed optimal conditions for robust synthesis of this enzyme.

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Section: Introductionmentioning

confidence: 99%

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Molecular cloning, expression, and characterization of acyltransferase from Pseudomonas protegens

Schmidt

Żądło‐Dobrowolska

Ruppert

et al. 2018

Appl Microbiol Biotechnol

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The formation of C-C bonds by using CoA independent acyltransferases may have significant impact for novel methods for biotechnology. We report the identification of Pseudomonas strains with CoA-independent acyltransferase activity as well as the heterologous expression of the enzyme in E. coli. The cloning strategies and selected expression studies are discussed. The recombinant acyltransferases were characterized with regard to thermal and storage stability, pH,- and co-solvent tolerance. Moreover, the impact of bivalent metals, inhibitors, and other additives was tested. Careful selection of expression and working conditions led to obtain recombinant acyltransferase form Pseudomonas protegens with up to 11 U mL−1 activity.Electronic supplementary materialThe online version of this article (10.1007/s00253-018-9052-z) contains supplementary material, which is available to authorized users.

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“…Perhaps this differentiation will become obsolete in the future. In recent years we have seen an explosion of novel reactions catalyzed by enzymes . The combination of a computational and an experimental approach has become state‐of‐the‐art, which, guided by scientific analysis, enables the design and development of improved catalysts.…”

Section: Au Revoir Uwe Bornscheuermentioning

confidence: 99%