Tuning auto-inducible pathway-independent dynamic switches for the optimisation of the microbial production of partially acetylated chitooligosaccharides

Thanks to the growing fields of synthetic biology, bioinformatics and systems biology, the number of applications of industrial biotechnology is rapidly expanding, contributing to the transition towards a bioeconomy. Additionally, new-to-nature compounds have been commercialised using biotechnology, showing its enormous potential. However, the engineered synthetic pathways compete with the host’s cellular metabolism and resources, thus limiting product yields and affecting cell growth. Therefore, it is more beneficial to delay expression of the novel introduced synthetic pathways or downregulate competing essential pathways at a certain timepoint in the cultivation, yielding a so-called two-phase fermentation. In this context, genetic circuitry allowing self-regulation and redirection of pathway fluxes based on bacterial autoinducer systems like quorum sensing (QS) could cope with this complexity. Despite several recent success stories using QS-based switches, there is still a need for a fine-tuned system that can accommodate the shape of the output response curve, the level of expression and the timing required for specific applications. The fine-tuned QS-switch will be applied for the microbial production of partially deacetylated chitooligosaccharides (paCOS) as proof of concept. These paCOS molecules are rising in popularity due to their numerous applications in healthcare, pharma, feed and food sectors.