New Stetter reactions catalyzed by thiamine diphosphate dependent MenD from E. coli

Beigi, Maryam; Waltzer, Simon; Zarei, Mostafa; Müller, Michael

doi:10.1016/j.jbiotec.2014.07.451

Cited by 19 publications

(13 citation statements)

References 25 publications

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“…This observation is most likely due to the higher promiscuous activity observed at 37°C. While approaches like this can provide an understanding of the promiscuous capabilities of enzymes (Beigi et al, ; Venkitasubramanian et al, ), an intensive kinetic analysis will require exploring activities over a range of substrate concentrations.…”

Section: Resultsmentioning

confidence: 99%

Characterizing and predicting carboxylic acid reductase activity for diversifying bioaldehyde production

Moura

Pertusi

Lenzini

et al. 2015

Biotech & Bioengineering

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Chemicals with aldehyde moieties are useful in the synthesis of polymerization reagents, pharmaceuticals, pesticides, flavors, and fragrances because of their high reactivity. However, chemical synthesis of aldehydes from carboxylic acids has unfavorable thermodynamics and limited specificity. Enzymatically catalyzed reductive bioaldehyde synthesis is an attractive route that overcomes unfavorable thermodynamics by ATP hydrolysis in ambient, aqueous conditions. Carboxylic acid reductases (Cars) are particularly attractive, as only one enzyme is required. We sought to increase the knowledge base of permitted substrates for four Cars. Additionally, the Lys2 enzyme family was found to be mechanistically the same as Cars and two isozymes were also tested. Our results show that Cars prefer molecules where the carboxylic acid is the only polar/charged group. Using this data and other published data, we develop a support vector classifier (SVC) for predicting Car reactivity and make predictions on all carboxylic acid metabolites in iAF1260 and Model SEED.

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Section: Resultsmentioning

confidence: 99%

Characterizing and predicting carboxylic acid reductase activity for diversifying bioaldehyde production

Moura

Pertusi

Lenzini

et al. 2015

Biotech & Bioengineering

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“…Also surprisingly atypical are Stetter reactions conducted on the α,β‐unsaturated ester substrates considered precursors for the desired acetylated ketones 1 . A reaction traditionally performed neat, in ethanol, or DMF at elevated temperatures, the Stetter reaction and other NHC‐catalyzed reactions can be made more amenable to conditions favorable to enzymes . We have previously demonstrated the viability of a decarboxylation‐enabled Stetter reaction under buffered aqueous conditions, though the elevated temperatures required for the generation of the Breslow intermediate would be deleterious to paired enzymes .…”

Section: Methodsmentioning

confidence: 99%

A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ‐Lactones

Maskeri

Schrader

Scheidt

2020

Chemistry A European J

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Combining biological and small-molecule catalysts under ac hemoenzymaticm anifold presents as eries of significant advantages to the synthetic community. We report herein the successful development of at wo-step/ single flask synthesis of g-lactones through the merger of Umpolung catalysis with ak etoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization.T his combined approach delivers highly enantio-and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.Scheme1.Existing strategies and proposed combined catalysiss trategy.[a] M.

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“…It is nowadays possible to carry out reactions catalyzed by enzymes with unnatural substrates, and by doing so, to gain access to new molecules that cannot be found in nature. One of such enzymes is MenD 7 as it provides biocatalytic access to new types of products not related to the products currently accessible by thiamine diphosphate (ThDP) dependent enzyme catalysis 8,9 . For further growth and development of biocatalysis, biochemical-engineering approaches can be very beneficial.…”

Section: Application Of Chemical Engineering Methodology In Process Dmentioning

confidence: 99%

“…ACN ( Fig. 1), was first introduced in 2014 8 . The relevance of this reaction is in the potential application of COHA as a building block; the molecule contains a nitrile group, which can be used to synthesize other functional groups in a straightforward manner 20 .…”

Section: Application Of Chemical Engineering Methodology In Process Dmentioning

confidence: 99%

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Application of Chemical Engineering Methodology in Process Development: A Case Study of MenD-catalyzed Synthesis of 6-Cyano-4-oxohexanoic Acid

Sudar

Dejanović

Müller

et al. 2019

Chem.Biochem.Eng.Q.

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To speed up evaluation, development and upscaling of new processes, the use of engineering methodology can have a great impact. Here we show the application of an engineering approach to find the reaction conditions allowing the best process metrics. An experimentally validated mathematical model for the MenD-catalyzed synthesis of a commercially unavailable product, 6-cyano-4-oxohexanoic acid, with a potential industrial use as a building block, was used for process optimization. Using the optimized conditions, 62.4 g dm-3 of product, volume productivity of 87.1 g dm-3 d-1 , product yield of 96 %, and biocatalyst productivity of 25.8 kg P kg-1 MenD can be achieved. Based on the optimized production procedure, economic analysis was performed to determine minimal product price required for project to be profitable in 8 years economic lifetime. In addition, Monte Carlo analysis (MCA) was used to assess the influence of uncertainties in estimation of input variables on overall economic performance.

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New Stetter reactions catalyzed by thiamine diphosphate dependent MenD from E. coli

Cited by 19 publications

References 25 publications

Characterizing and predicting carboxylic acid reductase activity for diversifying bioaldehyde production

Characterizing and predicting carboxylic acid reductase activity for diversifying bioaldehyde production

A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ‐Lactones

Application of Chemical Engineering Methodology in Process Development: A Case Study of MenD-catalyzed Synthesis of 6-Cyano-4-oxohexanoic Acid

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