GASB

Dr. Steffen Klamt

Analysis and Redesign of Biological Networks, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg , Germany

 

Title: Computational Design of Metabolic Networks and Applications to Engineer E. coli Cell Factories

Computational methods have become an important tool for metabolic engineering and rational
design of microbial cell factories to optimize fermentation processes. In my talk I will present
recent contribution of us in this field:

(1) Minimal cut set based algorithms for computational strain design [1,2].

(2) A large-scale computational study on the general feasibility of strain designs based on coupling of growth with product synthesis [3,4].

(3) Design and construction of an E. coli strain for high-yield production of itaconic acid reaching highest yields and titers that have ever been reported for heterologous itaconic acid production [5].

(4) The potential of two-stage production processes based on dynamic (synthetic) regulation of metabolic pathways and an application example for increasing the volumetric productivity of itaconic acid production by E. coli [6].

(5) Increasing the substrate utilization rate as a key challenge to implement efficient (two-stage) production processes with separated growth and production phase [7].

[1] von Kamp A, Klamt S (2014) Enumeration of smallest intervention strategies in genome-scale metabolic networks. PLoS Computational Biology 10(1):e1003378.

[2] Mahadevan R, von Kamp A, Klamt S (2015) Genome-scale strain designs based on regulatory minimal cut sets. Bioinformatics 31:2844-2851.

[3] Klamt S, Mahadevan R (2015) On the feasibility of growth-coupled product synthesis in microbial strains. Metabolic Engineering 30:166-178.

[4] von Kamp A, Klamt S. (2017) Growth-coupled overproduction is feasible for almost all metabolites in five major production organisms. Nature Communications 8: 15956.

[5] Harder B-J, Bettenbrock K, Klamt S (2016) Model-Based metabolic engineering enables high yield itaconic acid production by Escherichia coli. Metabolic Engineering 38:29-37.

[6] Harder BJ, Bettenbrock K, Klamt S. (2017) Temperature-dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli. Biotechnology and Bioengineering, in press.

[7] Klamt S, Mahadevan R, Hädicke O (2017) When do two-stage processes outperform one-stage processes? Biotechnology Journal , in press.