Pressurized CO<sub>2</sub> as a carboxylating agent for the biocatalytic <i>ortho</i>-carboxylation of resorcinol

Plasch, Katharina; Hofer, Gerhard; Keller, Walter; Hay, Sam; Heyes, Derren J.; Dennig, Alexander; Glueck, Silvia M.; Faber, Kurt

doi:10.1039/c8gc00008e

Cited by 25 publications

(30 citation statements)

References 41 publications

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“…As alternative CO 2 source to bicarbonate, gaseous carbon dioxide under pressure (~30–40 bar) was recently successfully employed for the carboxylation of resorcinol (1,3-dihydroxybenzene) with conversion of up to 68% by o -benzoic acid decarboxylases (Plasch et al, 2018). Attempts to carboxylate uracil ( 1b ) by IDCase using pressurized CO 2 (30 bar) were unsuccessful.…”

Section: Resultsmentioning

confidence: 99%

Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase: A Combined Theoretical and Experimental Study

et al. 2018

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The C-C bond cleavage catalyzed by metal-dependent iso-orotate decarboxylase (IDCase) from the thymidine salvage pathway is of interest for the elucidation of a (hypothetical) DNA demethylation pathway. IDCase appears also as a promising candidate for the synthetic regioselective carboxylation of N-heteroaromatics. Herein, we report a joint experimental-theoretical study to gain insights into the metal identity, reaction mechanism, and substrate specificity of IDCase. In contrast to previous assumptions, the enzyme is demonstrated by ICPMS/MS measurements to contain a catalytically relevant Mn2+ rather than Zn2+. Quantum chemical calculations revealed that decarboxylation of the natural substrate (5-carboxyuracil) proceeds via a (reverse) electrophilic aromatic substitution with formation of CO2. The occurrence of previously proposed tetrahedral carboxylate intermediates with concomitant formation of HCO3- could be ruled out on the basis of prohibitively high energy barriers. In contrast to related o-benzoic acid decarboxylases, such as γ-resorcylate decarboxylase and 5-carboxyvanillate decarboxylase, which exhibit a relaxed substrate tolerance for phenolic acids, IDCase shows high substrate fidelity. Structural and energy comparisons suggest that this is caused by a unique hydrogen bonding of the heterocyclic natural substrate (5-carboxyuracil) to the surrounding residues. Analysis of calculated energies also shows that the reverse carboxylation of uracil is impeded by a strongly disfavored uphill reaction.

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Section: Resultsmentioning

confidence: 99%

Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase: A Combined Theoretical and Experimental Study

et al. 2018

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“…In order to drive the equilibrium towards the energetically disfavored carboxylation direction, an excess of bicarbonate (usually 2–3 M) is most commonly applied as CO 2 source, alternatively pressurized (∼30 bar) or sub‐/supercritical carbon dioxide is used to a minor extent.…”

Section: Biocatalytic (De)carboxylation Of (Hetero)aromatics and αβ‐mentioning

confidence: 99%

Non‐Oxidative Enzymatic (De)Carboxylation of (Hetero)Aromatics and Acrylic Acid Derivatives

2019

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The utilization of carbon dioxide as a C 1 ‐building block for the production of valuable chemicals has recently attracted much interest. Whereas chemical CO 2 fixation is dominated by C−O and C−N bond forming reactions, the development of novel concepts for the carboxylation of C‐nucleophiles, which leads to the formation of carboxylic acids, is highly desired. Beside transition metal catalysis, biocatalysis has emerged as an attractive method for the highly regioselective (de)carboxylation of electron‐rich (hetero)aromatics, which has been recently further expanded to include conjugated α,β‐unsaturated (acrylic) acid derivatives. Depending on the type of substrate, different classes of enzymes have been explored for (i) the ortho ‐carboxylation of phenols catalyzed by metal‐dependent ortho ‐benzoic acid decarboxylases and (ii) the side‐chain carboxylation of para ‐hydroxystyrenes mediated by metal‐independent phenolic acid decarboxylases. Just recently, the portfolio of bio‐carboxylation reactions was complemented by (iii) the para ‐carboxylation of phenols and the decarboxylation of electron‐rich heterocyclic and acrylic acid derivatives mediated by prenylated FMN‐dependent decarboxylases, which is the main focus of this review. Bio(de)carboxylation processes proceed under physiological reaction conditions employing bicarbonate or (pressurized) CO 2 when running in the energetically uphill carboxylation direction. Aiming to facilitate the application of these enzymes in preparative‐scale biotransformations, their catalytic mechanism and substrate scope are analyzed in this review.

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“…It has been highlighted that carboxylation methods employing gaseous CO 2 as the carboxylating agent, instead of large excess of bicarbonate, can eliminate the need to use wasteful amount of bicarbonate salts [87] . In addition, carboxylation using pressurized CO 2 may simplify downstream reaction work‐up and product isolation.…”

Section: Strategies To Improve Carboxylation Yieldsmentioning

confidence: 99%

Synthetic Enzyme‐Catalyzed CO₂ Fixation Reactions

et al. 2021

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In recent years, (de)carboxylases that catalyze reversible (de)carboxylation have been targeted for application as carboxylation catalysts. This has led to the development of proof‐of‐concept (bio)synthetic CO2 fixation routes for chemical production. However, further progress towards industrial application has been hampered by the thermodynamic constraint that accompanies fixing CO2 to organic molecules. In this Review, biocatalytic carboxylation methods are discussed with emphases on the diverse strategies devised to alleviate the inherent thermodynamic constraints and their application in synthetic CO2‐fixation cascades.

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Pressurized CO₂ as a carboxylating agent for the biocatalytic ortho-carboxylation of resorcinol

Abstract: Utilization of gaseous carbon dioxide as a C1-building block in the biocatalytic ortho-carboxylation of a phenol.

Cited by 25 publications

References 41 publications

Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase: A Combined Theoretical and Experimental Study

Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase: A Combined Theoretical and Experimental Study

Non‐Oxidative Enzymatic (De)Carboxylation of (Hetero)Aromatics and Acrylic Acid Derivatives

Synthetic Enzyme‐Catalyzed CO₂ Fixation Reactions

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Pressurized CO2 as a carboxylating agent for the biocatalytic ortho-carboxylation of resorcinol

Abstract: Utilization of gaseous carbon dioxide as a C1-building block in the biocatalytic ortho-carboxylation of a phenol.

Cited by 25 publications

References 41 publications

Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase: A Combined Theoretical and Experimental Study

Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase: A Combined Theoretical and Experimental Study

Non‐Oxidative Enzymatic (De)Carboxylation of (Hetero)Aromatics and Acrylic Acid Derivatives

Synthetic Enzyme‐Catalyzed CO2 Fixation Reactions

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Pressurized CO₂ as a carboxylating agent for the biocatalytic ortho-carboxylation of resorcinol

Synthetic Enzyme‐Catalyzed CO₂ Fixation Reactions