Thioester-mediated biocatalytic amide bond synthesis with in situ thiol recycling

Schnepel, Christian; Pérez, Laura Rodríguez; Yu, Yuqi; Angelastro, Antonio; Heath, Rachel S.; Lubberink, Max; Falcioni, Francesco; Mulholland, Keith R.; Hayes, Martin A.; Turner, Nicholas J.; Flitsch, Sabine L.

doi:10.1038/s41929-022-00889-x

Cited by 29 publications

(26 citation statements)

References 59 publications

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“…Further exploiting CAR-A as a universal CoA-thioester synthetase, the system was coupled to a lysine acetyltransferase to achieve acylation of histone-derived peptide H4–20 including non-natural bio-orthogonal groups amenable to further ‘click chemistry’. 74…”

Section: Amidation Of Carboxylic Acidsmentioning

confidence: 99%

“…73 Recently, it was found that besides using an amine nucleophile to intercept the adenylate intermediate in the CAR-A reactions discussed previously, CAR-A was able to couple a wide variety of carboxylic acids to thiols, in particular CoA-SH, generating a range of CoA-thioesters and thus serving as a universal CoA ligase. 74 This general acyl-S-CoA recycling system can be used in situ with substoichiometric amounts of thiol and is an attractive alternative to chemical ligation strategies. 45,74 Coupling the CAR-A mediated CoA-ester synthesis to a complementary NAT enzyme, the system was exploited to synthesize an exceptionally wide range of amide products, including a set of amides derived from a variety of anilines like 52, which are usually regarded as more challenging substrates because of their low nucleophilicity and are not accessible through the direct CAR-A amidation method (Scheme 9B).…”

Section: Amidations Involving Coenzyme Amentioning

confidence: 99%

“…74 This general acyl-S-CoA recycling system can be used in situ with substoichiometric amounts of thiol and is an attractive alternative to chemical ligation strategies. 45,74 Coupling the CAR-A mediated CoA-ester synthesis to a complementary NAT enzyme, the system was exploited to synthesize an exceptionally wide range of amide products, including a set of amides derived from a variety of anilines like 52, which are usually regarded as more challenging substrates because of their low nucleophilicity and are not accessible through the direct CAR-A amidation method (Scheme 9B). Selected examples were performed on a preparative scale, demonstrating the value of this approach for synthesis.…”

Section: Amidations Involving Coenzyme Amentioning

confidence: 99%

“…B) CAR-A has been shown to accept CoA as a nucleophile and, because of its wide substrate scope, is able to serve as a universal CoA ligase. Therefore, CAR-A can be utilized in a comparable strategy when coupled to a NAT, forming a variety of amides 74.…”

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confidence: 99%

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Biocatalytic amide bond formation

2023

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Section: Amidation Of Carboxylic Acidsmentioning

confidence: 99%

Section: Amidations Involving Coenzyme Amentioning

confidence: 99%

Section: Amidations Involving Coenzyme Amentioning

confidence: 99%

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confidence: 99%

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Biocatalytic amide bond formation

2023

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“…As with ATP recycling, CoA recycling allows for use of CoA and truncated derivatives in sub-stoichiometric quantities for acylation of lysine residues in a histone-derived peptide with non-native amine donors. 42 Some amide bond forming enzymes catalyze the intermolecular reaction between two unprotected amino acids. 43 The lack of homo-dimerization in these reactions highlights the inherent selectivity of these enzymes.…”

Section: Carboxylic Amide Formationmentioning

confidence: 99%

Non-Native Site-Selective Enzyme Catalysis

Mondal

Snodgrass

Gomez

et al. 2023

Preprint

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The ability to a site-selectively modify equivalent functional groups in a molecule has the potential to streamline syntheses and increase product yields by lowering step counts. Enzymes catalyze site-selective transformations throughout primary and secondary metabolism, but leveraging this capability for non-native substrates and reactions requires a detailed understanding of the potential and limitations of enzyme catalysis and how these bounds can be extended by protein engineering. In this review, we discuss representative examples of site-selective enzyme catalysis involving functional group manipulation and C-H bond functionalization. We include illustrative examples of native catalysis, but our focus is on cases involving non-native substrates and reactions often using engineered enzymes. We then discuss the use of these enzymes for chemoenzymatic transformations and target-oriented synthesis and conclude with a survey of tools and techniques that could expand the scope of non-native site-selective enzyme catalysis.

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Reagent Engineering for Group Transfer Biocatalysis

Reed,

Seebeck

2023

Angewandte Chemie

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Biocatalysis has become a major driver in the innovation of preparative chemistry. Enzyme discovery, engineering and computational design have matured to reliable strategies in the development of biocatalytic processes. By comparison, substrate engineering has received much less attention. In this Minireview, we highlight the idea that the design of synthetic reagents may be an equally fruitful and complementary approach to develop novel enzyme‐catalysed group transfer chemistry. This Minireview discusses key examples from the literature that illustrate how synthetic substrates can be devised to improve the efficiency, scalability and sustainability, as well as the scope of such reactions. We also provide an opinion as to how this concept might be further developed in the future, aspiring to replicate the evolutionary success story of natural group transfer reagents, such as adenosine triphosphate (ATP) and S‐adenosyl methionine (SAM).

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Thioester-mediated biocatalytic amide bond synthesis with in situ thiol recycling

Cited by 29 publications

References 59 publications

Biocatalytic amide bond formation

Biocatalytic amide bond formation

Non-Native Site-Selective Enzyme Catalysis

Reagent Engineering for Group Transfer Biocatalysis

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