49 research outputs found

    The selective addition of water

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    Water is omnipresent and essential. Yet at the same time it is a rather unreactive molecule. The direct addition of water to C[double bond, length as m-dash]C double bonds is therefore a challenge not answered convincingly. In this perspective we critically evaluate the selectivity and the applicability of the different catalytic approaches for water addition reactions: homogeneous, heterogeneous and bio-catalytic. Here we would like to discuss how to speed up water addition and even make it selective.BiotechnologyApplied Science

    2-Deoxy-d-ribose-5-phosphate aldolase (DERA): applications and modifications

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    © 2018, The Author(s). 2-Deoxy-d-ribose-5-phosphate aldolase (DERA) is a class I aldolase that offers access to several building blocks for organic synthesis. It catalyzes the stereoselective C–C bond formation between acetaldehyde and numerous other aldehydes. However, the practical application of DERA as a biocatalyst is limited by its poor tolerance towards industrially relevant concentrations of aldehydes, in particular acetaldehyde. Therefore, the development of proper experimental conditions, including protein engineering and/or immobilization on appropriate supports, is required. The present review is aimed to provide a brief overview of DERA, its history, and progress made in understanding the functioning of the enzyme. Furthermore, the current understanding regarding aldehyde resistance of DERA and the various optimizations carried out to modify this property are discussed.ChemE/Product and Process EngineeringBT/BiocatalysisBT/Biotechnolog

    Biocatalysis making waves in organic chemistry

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    Biocatalysis has an enormous impact on chemical synthesis. The waves in which biocatalysis has developed, and in doing so changed our perception of what organic chemistry is, were reviewed 20 and 10 years ago. Here we review the consequences of these waves of development. Nowadays, hydrolases are widely used on an industrial scale for the benign synthesis of commodity and bulk chemicals and are fully developed. In addition, further enzyme classes are gaining ever increasing interest. Particularly, enzymes catalysing selective C-C-bond formation reactions and enzymes catalysing selective oxidation and reduction reactions are solving long-standing synthetic challenges in organic chemistry. Combined efforts from molecular biology, systems biology, organic chemistry and chemical engineering will establish a whole new toolbox for chemistry. Recent developments are critically reviewed.BT/Biocatalysi

    Veilige en Duurzame Biochemie met Blauwzuur?

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    Dit verslag geeft de bevindingen weer van een kortlopend onderzoek naar het gebruik van waterstofcyanide (HCN), ook wel Blauwzuur genaamd, in het veld van de (bio)chemie. In dit verslag worden de toxische eigenschappen van deze chemische stof afgewogen tegen veiligheidsaspecten vanuit het kader van Safe-by-Design gebruik makende van Inherent Safety Principles (ISPs).BT/Biotechnology and SocietyBT/Biocatalysi

    Novel oleate hydratases and potential biotechnological applications

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    Oleate hydratase catalyses the addition of water to the CC double bond of oleic acid to produce (R)-10-hydroxystearic acid. The enzyme requires an FAD cofactor that functions to optimise the active site structure. A wide range of unsaturated fatty acids can be hydrated at the C10 and in some cases the C13 position. The substrate scope can be expanded using ‘decoy’ small carboxylic acids to convert small chain alkenes to secondary alcohols, albeit at low conversion rates. Systematic protein engineering and directed evolution to widen the substrate scope and increase the conversion rate is possible, supported by new high throughput screening assays that have been developed. Multi-enzyme cascades allow the formation of a wide range of products including keto-fatty acids, secondary alcohols, secondary amines and α,ω-dicarboxylic acids. Key points: • Phylogenetically distinct oleate hydratases may exhibit mechanistic differences. • Protein engineering to improve productivity and substrate scope is possible. • Multi-enzymatic cascades greatly widen the product portfolio.BT/Biocatalysi

    Assessing the thiamine diphosphate dependent pyruvate dehydrogenase E1 subunit for carboligation reactions with aliphatic ketoacids

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    The synthetic properties of the Thiamine diphosphate (ThDP)-dependent pyruvate dehydrogenase E1 subunit from Escherichia coli (EcPDH E1) was assessed for carboligation reactions with aliphatic ketoacids. Due to its role in metabolism, EcPDH E1 was previously characterised with respect to its biochemical properties, but it was never applied for synthetic purposes. Here, we show that EcPDH E1 is a promising biocatalyst for the production of chiral α-hydroxyketones. WT EcPDH E1 shows a 180–250-fold higher catalytic efficiency towards 2-oxobutyrate or pyruvate, respectively, in comparison to engineered transketolase variants from Geobacillus stearothermophilus (TKGST). Its broad active site cleft allows for the efficient conversion of both (R)-and (S)-configured α-hydroxyaldehydes, next to linear and branched aliphatic aldehydes as acceptor substrates under kinetically controlled conditions. The alternate, thermodynamically controlled self-reaction of aliphatic aldehydes was shown to be limited to low levels of conversion, which we propose to be due to their large hydration constants. Additionally, the thermodynamically controlled approach was demonstrated to suffer from a loss of stereoselectivity, which makes it unfeasible for aliphatic substrates.BT/Biocatalysi

    Rhodococcus as A Versatile Biocatalyst in Organic Synthesis

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    The application of purified enzymes as well as whole-cell biocatalysts in synthetic organic chemistry is becoming more and more popular, and both academia and industry are keen on finding and developing novel enzymes capable of performing otherwise impossible or challenging reactions. The diverse genus Rhodococcus offers a multitude of promising enzymes, which therefore makes it one of the key bacterial hosts in many areas of research. This review focused on the broad utilization potential of the genus Rhodococcus in organic chemistry, thereby particularly highlighting the specific enzyme classes exploited and the reactions they catalyze. Additionally, close attention was paid to the substrate scope that each enzyme class covers. Overall, a comprehensive overview of the applicability of the genus Rhodococcus is provided, which puts this versatile microorganism in the spotlight of further research.BT/Biocatalysi

    Enzyme-Catalyzed Synthesis of Esters in Water

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    MsAcT catalyzes the esterification of primary alcohols in water. When utilizing acid and alcohol as starting materials low yields dictated by thermodynamics were observed. However, with activated esters such as ethyl acetate and vinyl acetate very high yields of the desired ester can be achieved in combination with the appropriate alcohol. This study investigated both the intrinsic kinetic properties of MsAcT for the hydrolysis and transesterification of esters in water as well as the thermodynamics of the reaction. In comparison to the chemical or enzymatic ester synthesis using either toxic reagent, and harsh organic solvents, the MsAcT-catalyzed synthesis of esters of primary alcohols can be achieved efficiently in water without neutralization steps.BT/BiocatalysisEKL Processin

    Biocatalysis explained: From pharmaceutical to bulk chemical production

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    Biocatalysis is one of the most promising technologies for the sustainable synthesis of molecules for pharmaceutical, biotechnological and industrial purposes. From the gram to the ton scale, biocatalysis is employed with success. This is underpinned by the fact that the global enzyme market is predicted to increase from 7billionto7 billion to 10 billion by 2024. This review concentrates on showing the strong benefits that biocatalysis and the use of enzymes can provide to synthetic chemistry. Several examples of successful implementations of enzymes are discussed highlighting not only high-value pharmaceutical processes but also low-cost bulk products. Thus, biocatalytic methods make the chemistry more environmentally friendly and product specific.BT/Biocatalysi

    Laccase did it again: A scalable and clean regeneration system for NAD<sup>+</sup> and its application in the synthesis of 12-oxo-hydroxysteroids

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    The specific oxidation of 12α-OH group of hydroxysteroids is required for the preparation of cheno-and ursodeoxycholic acid (CDCA and UDCA, respectively). The C12 oxidation of hydroxysteroids into their 12-oxo derivatives can selectively be performed by employing 12α-hydroxysteroid dehydrogenases. These enzymes use NAD(P)+ as an electron acceptor, which has to be re-oxidized in a so-called “regeneration system”. Recently, the enzyme NAD(P)H oxidase (NOX) was applied for the regeneration of NAD+ in the enzymatic preparation of 12-oxo-CDCA from cholic acid (CA), which allows air to be used as an oxidant. However, the NOX system suffers from low activity and low stability. Moreover, the substrate loading is limited to 10 mM. In this study, the laccase/mediator system was investigated as a possible alternative to NOX, employing air as an oxidant. The laccase/mediator system shows higher productivity and scalability than the NOX system. This was proven with a preparative biotransformation of 20 g of CA into 12-oxo-CDCA (92% isolated yield) by employing a substrate loading of 120 mM (corresponding to 50 g/L). Additionally, the performance of the laccase/mediator system was compared with a classical ADH/acetone regeneration system and with other regeneration systems reported in literature.BT/Biocatalysi
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