Industrial productivity bottlenecks
The biotech industry manufactures enzymes for a plethora of applications from food production to pharmaceutical drugs. However, industrial-scale fermentations pose certain limitations to the commercial exploitation of biotechnology and require improvement in production efficiency. The EU-funded ATRIEM (Advanced training in industrial enzyme manufacturing) project focused on two such industrial fermentation bottlenecks, namely cellular heterogeneity and the secretion of heterologous enzymes. At the same time, it offered high-quality training in molecular and cellular microbiology techniques to early stage researchers alongside relevant experience in an industrial environment. To investigate how individual cells respond to high-level enzyme production, researchers constructed fluorescent promoter-reporter systems, which responded to different physiological and differentiation pathways. When placed in the fermentation of two model industrial enzymes, these systems enabled scientists to monitor gene expression. They observed that heterologous enzyme expression brought a production bottleneck, both at the population and single-cell levels, clearly indicating secretion stress. The impact of secretion stress on productivity was quantified in detail and results showed that heterologous and not native enzymes were responsible. This data emphasised the importance of co-evolution between a native enzyme and its natural host, and pointed to novel strategies for improving productivity. Furthermore, scientists discovered that the chromosomal location of the enzyme-expressing cassette directly correlated with production efficiency. Taken together, the activities of ATRIEM provided important industrially-relevant information on production bottlenecks. Building on this knowledge will lead to potentially novel strategies for improving biotech productivity.
Keywords
Biotech industry, ATRIEM, cellular heterogeneity, heterologous enzymes, chromosomal location
