The main areas of collaboration and mutual technology transfer between the Teaming partners will cover the three major host cell types used for cell factory engineering: bacteria, yeast, and mammalian (CHO) cells. The collaboration will be mutually beneficial, as the specific fields of expertise will be shared in both directions. The figurebelow expresses the matrix of collaborations between researchers from the CFB (light boxes) and the ECSB (dark boxes).The groups focused on three main model organism are clusters as follows: yeast – top left, mammalian top right, and the bacterial – bottom left cluster. The green lines show a selection of collaboration connections between the groups:
One of the examples of joint research projects involves development of synthetic phosphorylation circuits technology (MPToolbox – Multisite Phosphorylation Toolbox) for metabolic pathway optimization in cell factories. The group of Prof. Loog has developed a unique toolbox of multisite phosphorylation-based protein tags for fine tuning of target protein expression and localization in engineered producer strains, while the group of Prof. Jensen (DTU, Biosustain) has been designing metabolic switches for yeast on the transcriptional level. In the colalboration project, we will use the MPToolbox to achieve coordinated balance of biosynthetic pathway enzymes in yeast cell factories with the aim to increase the performance of the strains and mitigate toxic intermediates. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field because of the fast response time-scales and wide combinatorial possibilities.
The technologies developed in both groups will be combined for an increased efficiency and applied on a number of industrial test cases. The developed cell factories which have a high industrial potential will be further optimized in the larger scale fermenters at the Bioprocessing unit at CFB and the ECSB Pilot Plant.
The MPToolbox as a new technology platform for cell factory design will have a strong impact on Estonian economy. Estonian Centre of Synthetic Biology is aiming to become an important centre of excellence in cell factory design and optimization, and will be focused on using local lignocellulosic biomass from forest industry as substrate for cell factories producing high value chemicals.