Journal
ORGANIC PROCESS RESEARCH & DEVELOPMENT
Volume 22, Issue 9, Pages 1101-1114Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.oprd.8b00119
Keywords
Biocatalysis; Process Development; Kinetic Characterization; Bottleneck Identification
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Funding
- European Union (EU) project ROBOX under EU's Horizon 2020 Programme Research and Innovation actions [635734H2020-LEIT BIO-2014-1]
- European Union [266025]
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Process development for biocatalytic reactions is a complex task due to the required interaction of several different scientific disciplines. Additionally, there is a lack of standardized procedures for guiding development and for identifying the major process limitations in these systems. This work seeks to address this problem by providing a methodology based on a simple, systematic series of experiments. Application of the methodology helps identify the major bottleneck for process implementation, whether it be enzyme activity, enzyme stability, or substrate mass transfer. In addition, the underlying mechanism behind these limitations can also be inferred. The methodology is illustrated using a simulated reaction system and is also applied to three experimental case studies. This methodology provides a set of simple experiments that may be performed at an early stage of biocatalytic process development to guide effective improvement strategies, whether they be via protein engineering or reaction engineering. Ultimately, this should afford faster and more efficient implementation of biocatalysts in industrial processes.
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