Teaching an old dog new trick - engineering E. coli for new-to-nature metabolism

Microbiology Seminar Series

  • Date: Jan 25, 2021
  • Time: 16:00
  • Speaker: Dr. Markus Jeschek
  • ETH Zürich, Department of Biosystems Science and Engineering, Switzerland
  • Location: Zoom
  • Host: Prof. Dr. Tobias Erb
  • Contact: toerb@mpi-marburg.mpg.de

Substantial recent progress in biocatalysis, metabolic engineering and the reading and writing of DNA open
up a plethora of new possibilities to construct microbes for sustainable bioprocesses. While we are arguably
only seeing the onset of these technological developments, it is not presumptuous to predict that they will
critically shape the inevitably required transition towards a circular economy. In my talk, I will share some
of our humble previous and planned contributions to this exciting and highly ambitious endeavor.

To this end, we seek to develop enzymes with catalytic features not found amongst natural biological
systems. Our efforts on the assembly and directed evolution of artificial metalloenzymes in the periplasm
of E. coli are targeted towards expanding the available biocatalytic repertoire with transition-metal catalyzed
reactions1-3. Furthermore, we develop tools and techniques to rationally integrate such “new parts” into
higher-order systems to obtain efficient microbial cell factories for sustainable bioproduction. For instance,
we develop means to design smart ribosome binding site (RBS) libraries for efficient protein level
optimization4. More recently, my team has developed a novel experimental technique, which uses next-generation
sequencing to record sets of more than 108 sequence-function data pairs per experiment. In a
recent study, we have used this method for the ultradeep assessment of RBSs to train a deep learning model
that predicts their translation behavior with unprecedented accuracy5. Similarly, we are currently using the
approach to rationalize key techniques for the engineering of E. coli on all levels of the central dogma (DNA,
RNA, protein) and further plan on expanding it towards different applications in higher cells in the future.

[1] M. Jeschek, S. Panke, T.R. Ward. Trends in Biotechnol., 36:60-72 (2018).
[2] M. Jeschek et al. Nature 537:661-665 (2016).
[3] T. Vornholt et al. Sci. Adv. (in press, 2020).
[4] M. Jeschek, D. Gerngross, S. Panke. Nat. Commun. 7:11163 (2016).
[5] S. Höllerer et al. Nat. Commun. 11:3551 (2020).

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