Biotransformations in Pure Organic Medium: Organic Solvent‐Labile Enzymes in the Batch and Flow Synthesis of Nitriles

2020

Eur J Org Chem

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As both, continuous synthesis and (bio-)catalysis gained increasing interest in research as well as for industrial applications, ways for merging these fields enables novel opportunities for modern sustainable process development. In this contribution, an alternative approach for the application of immobilized enzymes in continuous flow processes is presented utilizing heterogeneous biocatalysts as a mobile phase. Based on superabsorber-entrapped enzymes and whole cells as a "fluid heterogeneous phase", a segmented hydrogel/organic

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneous Catalysts “on the Move”: Flow Chemistry with Fluid Immobilised (Bio)Catalysts

Adebar

2020

Eur J Org Chem

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“…Further process development and extension of this PBR methodology with superabsorber-based redox enzymes towards other applications in biocatalytic ketone reduction and related redox biotransformations are currently in progress. In addition, in general (and thus, also for other types of enzymes) this type of PBR methodology represents an alternative to the use of standard carrier-immobilized biocatalysts, and this system also offers the perspective for applications beyond isolated enzymes and, for example, for whole cell catalysts [51]. A glass reactor was filled with a layer of cotton (5 mm), then superabsorber (35 mg, Favor SXM 9155) was added.…”

Section: Parametermentioning

confidence: 99%

Flow Process for Ketone Reduction Using a Superabsorber-Immobilized Alcohol Dehydrogenase from Lactobacillus brevis in a Packed-Bed Reactor

Adebar

2019

Bioengineering

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Flow processes and enzyme immobilization have gained much attention over the past few years in the field of biocatalytic process design. Downstream processes and enzyme stability can be immensely simplified and improved. In this work, we report the utilization of polymer network-entrapped enzymes and their applicability in flow processes. We focused on the superabsorber-based immobilization of an alcohol dehydrogenase (ADH) from Lactobacillus brevis and its application for a reduction of acetophenone. The applicability of this immobilization technique for a biotransformation running in a packed bed reactor was then demonstrated. Towards this end, the immobilized system was intensively studied, first in a batch mode, leading to >90% conversion within 24 h under optimized conditions. A subsequent transfer of this method into a flow process was conducted, resulting in very high initial conversions of up to 67% in such a continuously running process.were described by further groups using carrier-bound ADH from Lactobacillus brevis (LB-ADH) in combination with a mobile aqueous phase [30], or magnetic nanoparticle-bound ADH [31]. In addition, Buehler et al. investigated intensively the use of ADH in aqueous/organic segmented flow systems. It was shown that emulsion formation could be eliminated, and enzymatic mass transfer-limited reactions can be enhanced [32]. Furthermore, different means of stabilization of this reaction system were investigated [33]. Very recently, our group published an improved downstream process by means of such a segmented flow process, illustrated using two different ADHs and substrates [34].In continuous processes using packed bed reactors (PBR), catalyst immobilization is a prerequisite. Also, downstream processes benefit from immobilization, as separation of the reaction mixture from the catalyst is easier, and the catalyst reusability is improved [35]. Moreover, both, operational, as well as storage stability of the catalyst can potentially be significantly increased. However, often a significant loss of enzymatic activity during the immobilization process represents a drawback, and the reproducible production of immobilized catalyst may be a further challenge [36]. Numerous techniques have been developed over the past years, which can be classified in the following three major methods: (a) binding to a solid support (carrier), (b) entrapment (encapsulation) in polymer networks, or (c) cross-linking in the form of cross-linked enzyme aggregates (CLEAs) or cross-linked enzyme crystals (CLECs) [35]. Recently, much progress in the field of enzyme immobilization has been made [37][38][39][40][41].In this work, the option of entrapment of enzymes in polymer networks has been chosen. Often for this purpose, organic polymers containing cavities, sol-gel-processed particles, or membranes are used. A special case is the use of superabsorbent polymers to immobilize the entire aqueous phase. [42,43]. In this case, the enzyme is immobilized in its native aqueous environment, whereby undesired interact...

“…In detail, our overall approach is based on the use of fatty acids as starting materials and after hydroformylation the corresponding aldehydes are formed, which are transformed into the aldoximes by spontaneous condensation with hydroxylamine. Then, aldoximes are dehydrated under formation of the resulting desired nitriles by means of an aldoxime dehydratase, which turned out to be versatile biocatalysts for this purpose [11][12][13]. Alternatively, the desired nitriles could be synthesized from aldoximes in a dehydration reaction catalyzed by a transition metal salt in the presence of a nitrile solvent, which acts as a co-substrate.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Bifunctional Molecules for the Production of Polymers Based on Unsaturated Fatty Acids as Bioderived Raw Materials

Hinzmann

Druhmann

2020

Sustainable Chemistry

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Currently, investigations of polymer-building blocks made from biorenewable feedstocks such as, for example, fatty acids, are of high interest for the chemical industry. An alternative synthesis of nitrile-substituted aliphatic carboxylic acids as precursors for ω-amino acids, which are useful to produce polymers, was investigated starting from biorenewable fatty acids. By hydroformylation of unsaturated fatty acids or unsaturated acids being accessible from unsaturated fatty acids by cross-metathesis reactions, aldehydes are formed. In this work, the hydroformylation of such unsaturated acids led to the formation of the corresponding aldehydes, which were afterwards converted with hydroxylamine to aldoximes. Subsequent dehydration by an aldoxime dehydratase as a biocatalyst or by CuII acetate led to the desired nitriles. Within this work, C7-, C9- and C11-carboxylic acids with a terminal nitrile functionality as well as a branched nitrile-functionalized stearate derivative were synthesized by means of this approach. As these nitriles serve as precursors for amino acids being suitable for polymerization, this work represents an alternative synthetic access to polyamide precursors, which starts directly from unsaturated fatty acids as biorenewable resources and avoids harsh reaction conditions as well as and by-product formation.