Biocatalytic Process Technology

BIOCATALYSIS

A key technology for the next generation of processes will be biocatalysis (the use of one or more enzymes or cells containing one or more enzymes for the production of chemicals, pharmaceuticals and fuels). Biocataltyic processes offer the advantage of un-paralleled selectivity under mild reaction conditions. Nevertheless when using biocatalysis on non-natural reactants rates are often low and conditions frequently sub-optimal. This has led to the development of improved enzymes via recombinant DNA technology.

At PROCESS we work with both academic and industrial partners who supply recombinant enzymes and cells for us to use and test in entirely new processes. In order to complement this we focus on the novel process concepts which are also required for the final effective implementation of such processes (especially where the reaction thermodynamics is unfavorable). The work is mostly experimental, based both in the laboratory (in miniaturized and scaled-down equipment) as well as the pilot plant.

Foto: Klaus Holsting

 In addition some research is focused on methodology to implement and develop biocatalytic processes in the most effective way including economic and environmental evaluations, which are essential to ensure the sustainability of such new processes. The sub-group currently works on several classes enzymes such as transaminases (for the synthesis of (chiral) amines), lipases (for the synthesis of biodiesel), oxidases and oxygenases (for the selective introduction of oxygen into molecules). Process concepts include multi-enzymatic processes, substrate feeding, in-situ product removal and multi-phase processes. The work is funded by several EC projects, including BIOINTENSE which we launched in 2012.

An excellent example of the type of research carried out in the biocatalysis sub-group is that of the work done with transaminases, where enormous progress has been made in the last year. Transaminases are one of the most effective ways of making optically pure chiral amines. In particular because the conditions used mean that protection and subsequent de-protection of functional groups is not required. Optically pure chiral amines are of great importance in the pharmaceutical industry. Indeed interest is such that in 2013 we will have helped organize the first international conference on the application of transaminases together with KTH (Stockholm, Sweden), with attendance of over 100 from Europe, USA and Japan.  

Particularly interesting in 2012 has been the completion of the first stage of work examining the thermodynamics of such reactions, which are frequently unfavorable in the synthetic direction (creating the chiral center). Shifting the equilibrium is a basic requirement for implementation and we have now learnt that a combination of approaches is required, such as use of an excess amine donor alongside selective and effective in-situ co-product removal (IScPR). In this case effective co-product removal means stripping of a volatile by-product (such as acetone) or selective enzymatic removal of a by-product (such as pyruvate). The enzymatic method in combination with an excess donor holds great promise. Alongside this much progress has been made on a methodology to help select the donor molecule, reactor and control technology for substrate and (co)product feeding and removal, respectively, based on modeling and fundamental data. The results have been published in a series of articles and at several international conferences in 2012 and more exciting results in this area can be expected within 2013.

Link to poster 

A rational approach for ω-transaminase-catalyzed process design:
synthesis of p-Br-1-phenylethylamine  

 

Design of an enzymatic FAEE-biodiesel process

 Enzymatic production of biodiesel: reaction engineering

Identification of bottlenecks for P450
biotransformation processes

 Miniaturized Experimental Toolbox for
ω-Transaminase Technology (BIOINTENSE)

Operation and Control of Enzymatic Biodiesel Pro

 

 

 Overcoming kinetic limitations in
ω-transaminase catalyzed reaction

Process development for multi-enzymatic
synthesis
 of sialic acid

Process strategies for implementing ω-transaminase
catalyzed reactions

 Process/Reactor selection for multi-step biocatalysis

 Reactor selection for multi-enzymatic processes

Simulation study of microbioreactor configurations for production
of optically pure chiral amines

Towards a standardized way of reporting physicochemical data and process
metrics for transaminase reactions

Towards an integrated μ-factory: Integrated Micro Membrane
packed bed reactor

Use of ‘windows of operation’ to guide process design
o
f ω-transaminase catalyzed reactions

 

 

Contact

John Woodley
Professor
DTU Chemical Engineering
+45 45 25 28 85