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Journal ArticleDOI

Overcoming the Incompatibility Challenge in Chemoenzymatic and Multi-Catalytic Cascade Reactions.

06 Feb 2018-Chemistry: A European Journal (John Wiley & Sons, Ltd)-Vol. 24, Iss: 8, pp 1755-1768
TL;DR: This Minireview will summarize recent synthetic examples of (chemo)enzymatic cascade reactions and outline promising methods for their spatial control either by using bio-derived or synthetic systems.
Abstract: Multi-catalytic cascade reactions bear a great potential to minimize downstream and purification steps, leading to a drastic reduction of the produced waste. In many examples, the compatibility of chemo- and biocatalytic steps could be easily achieved. Problems associated with the incompatibility of the catalysts and their reactions, however, are very frequent. Cascade-like reactions can hardly occur in this way. One possible solution to combine, in principle, incompatible chemo- and biocatalytic reactions is the defined control of the microenvironment by compartmentalization or scaffolding. Current methods for the control of the microenvironment of biocatalysts go far beyond classical enzyme immobilization and are thus believed to be very promising tools to overcome incompatibility issues and to facilitate the synthetic application of cascade reactions. In this Minireview, we will summarize recent synthetic examples of (chemo)enzymatic cascade reactions and outline promising methods for their spatial control either by using bio-derived or synthetic systems.
Citations
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Journal ArticleDOI
01 Jan 2018
TL;DR: This Review focuses on efforts to combine chemo- and biocatalysts, outlining the opportunities achievable by this approach and also efforts to overcome any incompatibilities between these different systems.
Abstract: The past decade has seen a substantial increase in successful examples of the combination of chemo- and biocatalysis for multistep syntheses. This is driven by obvious advantages such as higher yields, decreased costs, environmental benefits and high selectivity. On the downside, efforts must be undertaken to combine the divergent reaction conditions, reagent tolerance and solvent systems of these ‘different worlds of catalysis’. Owing to progress in enzyme discovery and engineering, as well as in the development of milder and more compatible conditions for operating with various chemocatalysts, many historical limitations can already be overcome. This Review highlights the opportunities available in the chemical space of combined syntheses using prominent examples, but also discusses the current challenges and emerging solutions, keeping in mind the fast progress in transition metal-, organo-, photo-, electro-, hetero- and biocatalysis. Chemical and biological catalysts provide distinct advantages and disadvantages to the synthetic chemist. This Review focuses on efforts to combine chemo- and biocatalysts, outlining the opportunities achievable by this approach and also efforts to overcome any incompatibilities between these different systems.

373 citations

Journal ArticleDOI
TL;DR: The most important recent developments in the field of biocatalytic oxidation chemistry are critically summarised and the most pressing bottlenecks as well as promising solutions are identified.
Abstract: Oxidation chemistry using enzymes is approaching maturity and practical applicability in organic synthesis. Oxidoreductases (enzymes catalysing redox reactions) enable chemists to perform highly selective and efficient transformations ranging from simple alcohol oxidations to stereoselective halogenations of non-activated C-H bonds. For many of these reactions, no "classical" chemical counterpart is known. Hence oxidoreductases open up shorter synthesis routes based on a more direct access to the target products. The generally very mild reaction conditions may also reduce the environmental impact of biocatalytic reactions compared to classical counterparts. In this Review, we critically summarise the most important recent developments in the field of biocatalytic oxidation chemistry and identify the most pressing bottlenecks as well as promising solutions.

302 citations

Journal ArticleDOI
TL;DR: An overview of the various approaches for using light in biocatalysis is given and enzymes with a light switchable moiety have been investigated to turn off/on or tune the actual reaction.
Abstract: Light has received increased attention for various chemical reactions but also in combination with biocatalytic reactions. Because currently only a few enzymatic reactions are known, which per se require light, most transformations involving light and a biocatalyst exploit light either for providing the cosubstrate or cofactor in an appropriate redox state for the biotransformation. In selected cases, a promiscuous activity of known enzymes in the presence of light could be induced. In other approaches, light-induced chemical reactions have been combined with a biocatalytic step, or light-induced biocatalytic reactions were combined with chemical reactions in a linear cascade. Finally, enzymes with a light switchable moiety have been investigated to turn off/on or tune the actual reaction. This Review gives an overview of the various approaches for using light in biocatalysis.

178 citations

Journal ArticleDOI
TL;DR: This review describes the choices of support materials and cross-linkers together with several mechanisms that influence the performance, stabilization and hyperactivation of immobilized enzymes.
Abstract: The primary means of immobilizing enzymes are to boost the enzyme productivity and operational stability, alongside facilitating the reuse of enzymes. Notwithstanding the aforementioned benefits, enzyme immobilization promotes high catalytic activity and stability, convenient handling of enzymes, in addition to their facile separation from reaction mixtures without contaminating the products. This review describes the choices of support materials and cross-linkers together with several mechanisms that influence the performance, stabilization and hyperactivation of immobilized enzymes. Altering enzyme properties often changes the enzyme structure due to random modifications in the behavior, which in some cases can be positive or negative. Future strategy to develop new generations of immobilized enzymes should capitalize on the rapid advances of genetic manipulation, organic chemistry, computational chemistry and bioinformatics, reactor and reaction design. Upcoming efforts to improve enzymes as industrial biocatalysts must consider their development for increased selective promiscuity suitable for multiple biotransformations, either independently or as catalytic cascade processes thereby enhance the cost-effectiveness of the processes.

137 citations

References
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Journal Article
01 Jan 2002-Science
TL;DR: Future applications of polymer vesicles will rely on exploiting unique property-performance relations, but results to date underscore the fact that biologically derived vesicle are but a small subset of what is physically and chemically possible.
Abstract: Vesicles are microscopic sacs that enclose a volume with a molecularly thin membrane. The membranes are generally self-directed assemblies of amphiphilic molecules with a dual hydrophilic-hydrophobic character. Biological amphiphiles form vesicles central to cell function and are principally lipids of molecular weight less than 1 kilodalton. Block copolymers that mimic lipid amphiphilicity can also self-assemble into vesicles in dilute solution, but polymer molecular weights can be orders of magnitude greater than those of lipids. Structural features of vesicles, as well as properties including stability, fluidity, and intermembrane dynamics, are greatly influenced by characteristics of the polymers. Future applications of polymer vesicles will rely on exploiting unique property-performance relations, but results to date already underscore the fact that biologically derived vesicles are but a small subset of what is physically and chemically possible.

2,423 citations

Journal ArticleDOI
14 May 1999-Science
TL;DR: The results suggest a new class of synthetic thin-shelled capsules based on block copolymer chemistry, and both the membrane bending and area expansion moduli of electroformed polymersomes (polymer-based liposomes) fell within the range of lipid membrane measurements.
Abstract: Vesicles were made from amphiphilic diblock copolymers and characterized by micromanipulation. The average molecular weight of the specific polymer studied, polyethyleneoxide-polyethylethylene (EO40-EE37), is several times greater than that of typical phospholipids in natural membranes. Both the membrane bending and area expansion moduli of electroformed polymersomes (polymer-based liposomes) fell within the range of lipid membrane measurements, but the giant polymersomes proved to be almost an order of magnitude tougher and sustained far greater areal strain before rupture. The polymersome membrane was also at least 10 times less permeable to water than common phospholipid bilayers. The results suggest a new class of synthetic thin-shelled capsules based on block copolymer chemistry.

2,338 citations

Journal ArticleDOI
TL;DR: This critical review summarises the different conditions which have been described to synthesise PCL, and gives a broad overview of the different catalytic systems that were used (enzymatic, organic and metal catalyst systems).
Abstract: Polycaprolactone (PCL) is an important polymer due to its mechanical properties, miscibility with a large range of other polymers and biodegradability. Two main pathways to produce polycaprolactone have been described in the literature: the polycondensation of a hydroxycarboxylic acid: 6-hydroxyhexanoic acid, and the ring-opening polymerisation (ROP) of a lactone: e-caprolactone (e-CL). This critical review summarises the different conditions which have been described to synthesise PCL, and gives a broad overview of the different catalytic systems that were used (enzymatic, organic and metal catalyst systems). A surprising variety of catalytic systems have been studied, touching on virtually every section of the periodic table. A detailed list of reaction conditions and catalysts/initiators is given and reaction mechanisms are presented where known. Emphasis is put on the ROP pathway due to its prevalence in the literature and the superior polymer that is obtained. In addition, ineffective systems that have been tried to catalyse the production of PCL are included in the electronic supplementary information for completeness (141 references).

1,247 citations

Journal ArticleDOI
TL;DR: For the industrial implementation of many transformations alternative methods are available and the advantages of the individual methods will be discussed herein and exemplified by syntheses of relevant compounds.
Abstract: Enantiomerically pure amino acids, amino alcohols, amines, alcohols, and epoxides play an increasingly important role as intermediates in the pharmaceutical industry and agrochemistry, where both a high degree of purity and large quantities of the compounds are required. The chemical industry has primarily relied upon established chemical methods for the synthesis of these intermediates, but is now turning more and more to enzymatic and biotechnological fermentation processes. For the industrial implementation of many transformations alternative methods are available. The advantages of the individual methods will be discussed herein and exemplified by syntheses of relevant compounds.

1,210 citations

Journal ArticleDOI
TL;DR: The approach followed here may lead to more productive and sustainable water treatment membranes, whereas the variable levels of permeability obtained with different concentrations of AqpZ may provide a key property for drug delivery applications.
Abstract: The permeability and solute transport characteristics of amphiphilic triblock-polymer vesicles containing the bacterial water-channel protein Aquaporin Z (AqpZ) were investigated. The vesicles were made of a block copolymer with symmetric poly-(2-methyloxazoline)-poly-(dimethylsiloxane)-poly-(2-methyloxazoline) (PMOXA15-PDMS110-PMOXA15) repeat units. Light-scattering measurements on pure polymer vesicles subject to an outwardly directed salt gradient in a stopped-flow apparatus indicated that the polymer vesicles were highly impermeable. However, a large enhancement in water productivity (permeability per unit driving force) of up to ≈800 times that of pure polymer was observed when AqpZ was incorporated. The activation energy (Ea) of water transport for the protein-polymer vesicles (3.4 kcal/mol) corresponded to that reported for water-channel-mediated water transport in lipid membranes. The solute reflection coefficients of glucose, glycerol, salt, and urea were also calculated, and indicated that these solutes are completely rejected. The productivity of AqpZ-incorporated polymer membranes was at least an order of magnitude larger than values for existing salt-rejecting polymeric membranes. The approach followed here may lead to more productive and sustainable water treatment membranes, whereas the variable levels of permeability obtained with different concentrations of AqpZ may provide a key property for drug delivery applications.

662 citations