Biocatalysed reduction of carboxylic acids to primary alcohols in aqueous medium: A novel synthetic capability of the zygomycete fungus Syncephalastrum racemosum

Carboxylic acid reductase enzymes (CARs) meet the demand in synthetic chemistry for a green and regiospecific route to aldehydes from their respective carboxylic acids. However, relatively few of these enzymes have been characterized. A sequence alignment with members of the ANL (Acyl‐CoA synthetase/ NRPS adenylation domain/Luciferase) superfamily of enzymes shed light on CAR functional dynamics. Four unstudied enzymes were selected by using a phylogenetic analysis of known and hypothetical CARs, and for the first time, a thorough biochemical characterization was performed. Kinetic analysis of these enzymes with various substrates shows that they have a broad but similar substrate specificity. Electron‐rich acids are favored, which suggests that the first step in the proposed reaction mechanism, attack by the carboxylate on the α‐phosphate of adenosine triphosphate (ATP), is the step that determines the substrate specificity and reaction kinetics. The effects of pH and temperature provide a clear operational window for the use of these CARs, whereas an investigation of product inhibition by NADP+, adenosine monophosphate, and pyrophosphate indicates that the binding of substrates at the adenylation domain is ordered with ATP binding first. This study consolidates CARs as important and exciting enzymes in the toolbox for sustainable chemistry and provides specifications for their use as a biocatalyst.

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“…This CAR is active against C 2 –C 18 fatty acids . CARs have also been reported in the fungi Syncephalastrum racemosum and Trametes versicolor …”

Section: Introductionmentioning

confidence: 81%

Characterization of Carboxylic Acid Reductases as Enzymes in the Toolbox for Synthetic Chemistry

et al. 2017

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“…1 H NMR (400 MHz, CDCl 3 ) d: 1.95 (s broad , 1H, OH), 3.97 (t, J ¼ 4.5 Hz, 2H, CH 2 ), 4.09 (t, J ¼ 4.5 Hz, 2H, CH 2 ), 6.92-6.99 (m, 3H, ArH), 7.30 (t, J ¼ 8 Hz, 2H, ArH). 25 4.2.2. General procedure for the direct synthesis of esters via PCC oxidative esterication.…”

Section: Methodsmentioning

confidence: 99%

Sequential alcohol oxidation/putative homo Claisen–Tishchenko-type reaction to give esters: a key process in accessing novel biologically active lactone macrocycles

et al. 2016

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We report an efficient methodology for the direct oxidative esterification of primary alcohols to diether-esters using pyridinium chlorochromate (PCC). Numerous studies were carried out to probe the reaction mechanism and at the same time optimize the reaction conditions. The reaction could be conducted with 1 equivalent of PCC and 1 equivalent of BF3.OEt2. Indications based on literature precident were that the reaction may proceed via a sequential alcohol oxidation to the aldehyde followed by a putative Cr catalyzed or Boron Claisen-Tishchenko-type reaction. Using this efficient methodology, we synthesized a family of novel diether-esters in very good yields; some of these molecules were subsequently tested against both acetylcholinesterase (AChE) and butyrlcholinesterase (BuChE). In addition, we also disclose a new synthetic strategy for the synthesis of lactam macrocycles with potential biological activity. This methodology included the regioselective borylation of the ester substrate and a subsequent Suzuki-Miyaura coupling to obtain the desired lactam macrocycle.

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“…Nature offers an immeasurable arsenal of biotechnological tools to transform a plethora of chemical compounds. In particular, the biotransformation of aromatic carboxylic acids is at the forefront [7,8]. Goodwin has compiled extensive data concerning the biotransformation of these molecules [9].…”

Section: Introductionmentioning

confidence: 99%

Self-sufficient redox biotransformation of lignin-related benzoic acids with Aspergillus flavus

Palazzolo

Mascotti

Lewkowicz

et al. 2015

Journal of Industrial Microbiology and Biotechnology

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Aromatic carboxylic acids are readily obtained from lignin in biomass processing facilities. However, efficient technologies for lignin valorization are missing. In this work, a microbial screening was conducted to find versatile biocatalysts capable of transforming several benzoic acids structurally related to lignin, employing vanillic acid as model substrate. The wild-type Aspergillus flavus growing cells exhibited exquisite selectivity towards the oxidative decarboxylation product, 2-methoxybenzene-1,4-diol. Interestingly, when assaying a set of structurally related substrates, the biocatalyst displayed the oxidative removal of the carboxyl moiety or its reduction to the primary alcohol whether electron withdrawing or donating groups were present in the aromatic ring, respectively. Additionally, A. flavus proved to be highly tolerant to vanillic acid increasing concentrations (up to 8 g/L), demonstrating its potential application in chemical synthesis. A. flavus growing cells were found to be efficient biotechnological tools to perform self-sufficient, structure-dependent redox reactions. To the best of our knowledge, this is the first report of a biocatalyst exhibiting opposite redox transformations of the carboxylic acid moiety in benzoic acid derivatives, namely oxidative decarboxylation and carboxyl reduction, in a structure-dependent fashion.

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Biocatalysed reduction of carboxylic acids to primary alcohols in aqueous medium: A novel synthetic capability of the zygomycete fungus Syncephalastrum racemosum

Cited by 11 publications

References 33 publications

Characterization of Carboxylic Acid Reductases as Enzymes in the Toolbox for Synthetic Chemistry

Characterization of Carboxylic Acid Reductases as Enzymes in the Toolbox for Synthetic Chemistry

Sequential alcohol oxidation/putative homo Claisen–Tishchenko-type reaction to give esters: a key process in accessing novel biologically active lactone macrocycles

Self-sufficient redox biotransformation of lignin-related benzoic acids with Aspergillus flavus

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