Professor John Woodley (Technical University of Denmark) introduced the vital topic of developing enabling technologies for commercialisation of industrial biotechnology processes at the event. Bioprocessing for chemicals and fuels manufacture covers both novel fermentation processes and biocatalytic conversions (whole cell and isolated (immobilised) enzymes) and opportunities for development exist in numerous areas, including integration with bio-refineries, retrofit of existing plants through novel integration, and producing materials based on glucose and glycerol. However, these are met with a number of implementation challenges including enzyme availability, stability under industrial conditions, thermodynamics and development time and cost. John explained that to overcome these challenges, multidisciplinary teams are required to bring together the equally important aspects of chemistry (catalyst selection and design), biology (enzyme technology) and chemical engineering (reactor and process design).
A number of FP7 projects, including BIONEXGEN and BIO-INTENSE, for which John is the co-ordinator, have brought together these multidisciplinary teams and led to a number of observations and developments to be achieved. Download Johnís presentation here.
John outlined a four stage potential strategy for process design:
1. Target setting. Measuring with the right metrics is vital. The measurement of economic and environmental performance will change depending on the definition of the process metric. For example, measuring biocatalyst yield (kg of product / kg of catalyst) will enable the economic performance to take account of the biocatalyst cost but not the cost of the raw material and the environmental performance with respect to energy use and c-source of producing the biocatalyst to be evaluated but not that of any downstream processing requirements.
2. Bottleneck identification. Once the targets are known measuring the various metric (biocatalyst yield (g product / g biocatalyst), reaction yield (g product / g substrate), space-time-yield (g/L/h) etc) under increasing biocatalyst concentrations will identify whether the reaction under investigation is stability limited, product limited or rate limited e.g:
3. Improvement Strategy. Once the bottleneck is known the improvement strategy can then be established. One approach is to identify the parameters which define the operating window. This can involve an evaluation of alternative economic scenarios, changing process variables, time-dependent effects, scale-dependent effects, changes to the biocatalyst, multi-enzymatic processes
4. Evaluation of options. The final stage of the process is to evaluate the options for improvement and often, considering a scale-down approach to process development is advantageous. However, the challenge is how to do this quickly with minimal reagents etc. In summary, John concluded that we need to recognize that there is not one single problem (e.g. inhibition and thermodynamics), nor one single solution (e.g. protein engineering and ISPR) and more needs to be understood about the limits for application of each intensification technology. Case-studies and demonstrations are needed to highlight success and to ensure the interface of chemistry, biology and engineering continues to come together. In order to develop novel solutions to these issues, bio-manufacturing technologies need to be taught in an integrated way with chemical engineering and biotechnology.