Carboxylic acid reductases enable intramolecular lactamization reactions

Qin, Zongmin; Zhang, Mengjie; Sang, Xianke; Zhang, Wuyuan; Qu, Ge; Sun, Zhoutong

doi:10.1016/j.gresc.2022.05.009

Cited by 11 publications

(5 citation statements)

References 51 publications

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“…[84] In case the amine donor is present on the carboxylate substrate itself, CARs can mediate lactam formation as shown first for MaCAR2 [85] and then for SruCAR and its phosphopantetheinyl attachment site mutant SruCAR S702A . [86] Likewise, MmCAR was also able to catalyze esterification of a variety of carboxylic acids and alcohols, albeit with lower yield compared to amidation. Similar to amidation, the MmCAR S685A (lacking the phosphopantetheinyl attachment site) and MmCAR Δ729-1175 variants mediated esterification, showing that the A-domain alone is sufficient for this purpose.…”

Section: Promiscuous Reactions Catalyzed By Cars or Car Domainsmentioning

confidence: 99%

Biocatalytic Carboxylate Reduction – Recent Advances and New Enzymes

Winkler

Ling

2022

ChemCatChem

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Carboxylate reductases (CARs) are valuable catalysts for the selective one‐step reduction of carboxylic acids to their corresponding aldehydes. In recent years, numerous new CARs have been made available, studied and applied in the context of biocatalytic syntheses. The preparation of aldehydes as end products for the flavor and fragrance sector and the integration of CARs in cascade reactions with aldehydes as the key intermediates represent the two major fields of applications. This review gives a comprehensive overview of the current toolbox of recombinant CARs and their numerous carboxylate substrates. Non‐natural functions of CARs are highlighted and recent insight into the structure‐function relationship of CARs are summarized.

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Section: Promiscuous Reactions Catalyzed By Cars or Car Domainsmentioning

confidence: 99%

Biocatalytic Carboxylate Reduction – Recent Advances and New Enzymes

Winkler

Ling

2022

ChemCatChem

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“…In contrast, enzymes catalyzing both steps of adenylation and amidation, such as in the former examples of CfaL and McbA ligases, are few and have not been identified for NAAA biosynthesis thus far. Similar mechanism was also observed in the truncated construct of carboxylic acid reductases (CAR‐A) catalyzing amide formation from fatty acid and amino alcohol, [14d] and in the intramolecular cyclization of ω‐amino acids to form lactams, [14e–f] all with good yields [14d–f] . Thus far, this enzyme has not yet been used for NAAA amide synthesis.…”

Section: Atp‐dependent Biosynthesis Of Naaa Amidesmentioning

confidence: 53%

Enzymatic Strategies for the Biosynthesis of N‐Acyl Amino Acid Amides

Kua,

Nguyen,

2024

ChemBioChem

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Amide bond‐containing biomolecules are functionally significant and useful compounds with diverse applications. For example, N‐acyl amino acids (NAAAs) are an important class of lipoamino acid amides with extensive use in food, cosmetic and pharmaceutical industries. Their conventional chemical synthesis involves the use of toxic chlorinating agents for carboxylic acid activation. Enzyme‐catalyzed biotransformation for the green synthesis of these amides is therefore highly desirable. Here, we review a range of enzymes suitable for the synthesis of NAAA amides and their strategies adopted in carboxylic acid activation. Generally, ATP‐dependent enzymes for NAAA biosynthesis are acyl‐adenylating enzymes that couple the hydrolysis of phosphoanhydride bond in ATP with the formation of an acyl‐adenylate intermediate. In contrast, ATP‐independent enzymes involve hydrolases such as lipases or aminoacylases, which rely on the transient activation of the carboxylic acid. This occurs either through an acyl‐enzyme intermediate or by favorable interactions with surrounding residues to anchor the acyl donor in a suitable orientation for the incoming amine nucleophile. Recently, the development of an alternative pathway involving ester‐amide interconversion has unraveled another possible strategy for amide formation through esterification‐aminolysis cascade reactions, potentially expanding the substrate scope for enzymes to catalyze the synthesis of a diverse range of NAAA amides.

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“…Using both wild-type and mutants of CAR from Segniliparus rugosus various substituted lactams of different ring sizes were synthesised with some examples showing stereoselectivity (Scheme 12D). 103 This lactamisation activity of CAR has also been applied in a one-pot biocatalytic cascade forming ε-caprolactam from cyclohexanol. 104…”

Section: Lactamisationmentioning

confidence: 99%

“…88 Using a different reductive amination strategy, an NADPH-dependent reductive aminase has been shown to catalyse the coupling of a keto ester with propargylamine, which then formed the (R)-lactam products in high yields and Using both wild-type and mutants of CAR from Segniliparus rugosus various substituted lactams of different ring sizes were synthesised with some examples showing stereoselectivity (Scheme 12D). 103 This lactamisation activity of CAR has also been applied in a one-pot biocatalytic cascade forming ε-caprolactam from cyclohexanol. 104…”

Section: Lactamisationmentioning

confidence: 99%