Heurisko culture automaton

Within the framework of a collaboration with Heurisko, a partner of the TWB consortium, two automated microbial culture systems – proprietary to the company – are installed on TWB’s Biotransformation and culture platform.

. The configuration of the reactors and surrounding fluidics permits evolutions of several months with a minimum risk of contamination. This evolution platform can be applied to the development of non-GMO strains or to the development of metabolically or genetically engineered strains. The tool is compatible with

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conditions. It makes it possible to grow continuous evolution cultures with an automation of operations that are conventionally performed by an operator. The system, designed so as to limit to a minimum any wearing part, allows for a very long culture duration (>6 months) without any risk of contamination or hardware failure. The low volume of culture (<10 mL) decreases the amounts of medium to be prepared and makes possible the use of expensive constituents. One advantage among many others is the

during evolution. This pitfall systematically encountered in conventional evolution chemostats is avoided by various innovations of the system. Dilution is at the heart of the mode of controlling the selection of the various sub-populations in the continuous culture. The type and level of selection pressure are automatically controlled by the dilution speed and the composition of the culture medium or media. Different culture protocols are available:

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, to optimise exploitation of the substrate, productivity, and resistance to stress of an element of the medium (substrate, product, co-product), respectively. The objective of the evolution strategy can also be the in vivo introduction of new biological functions or new metabolic pathways. The aims can also be purely scientific such as understanding metabolic pathways, regulation loops, etc. Many barriers have been overcome in real cases by the Heurisko technology:

• Adaptation of a wild E. coli strain to the presence of a 20 g.L-1 concentration of n-butanol in 250 days
• Recovery of a prototrophy to histidine by a new synthesis pathway in less than 4 months
• Substitution of the thymine base (T) by its synthetic analogue 5-chlorouracil (X) in the DNA alphabet of an engineered strain in 170 days.

The innovative Heurisko technology perfectly complements TWB’s range of services. This system provides an original solution for improving the performance of culture processes, adapting non-GMO strains to the stresses of industrial conditions and increasing the robustness of newly engineered strains. TWB wishes to make this new tool as accessible as possible, within the framework of a simple service (optimisation of a strain of interest) or of an integrated project for the

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