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Two-Step-Strategy towards an Orthogonal Bio-System

Objective

The integration of orthogonality is a crucial research strategy in the rational design of biological systems for novel applications. In order to produce such highly predictable orthogonal systems, we propose to employ cell-free systems of highly engineered composition generated from living cells, which are complex enough to reproduce the major synthetic capabilities of living cells - such as the synthesis of natural and artificial saccharides - but are simplified enough to come close to truly engineerable systems. We propose a two-step-strategy: In a first step, the protein synthesis of a growing bacterial cell will be channeled solely to a limited set of system components with the help of the RNA-interferase MazF. In a second step, the cells will be homogenized and the resulting cell-free extract, already enriched in the required protein components, will be subjected to selective hydrolysis of predefined proteins, which otherwise would connect the designed system to the remaining protein background, which would make the performance of the complex system unpredictable. As a proof-of-concept, we propose to implement a preparative 12-step synthesis from cheap glucose and N-acetyl-glucosamine to a valuable antiviral-precursor, N-acetyl-neuraminic acid.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

FP7-PEOPLE-2011-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Address
Raemistrasse 101
8092 Zuerich
Switzerland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 184 709,40
Administrative Contact
Sven Panke (Prof.)