SYNMOD

Duration: 36 months

Coordinator: Prof. Oscar Kuipers, University of Groningen (the Netherlands)

Contact Person:

Prof. Oscar Kuipers
Room 6514.0022b
Kerklaan 30
9751 NN Haren, The Netherlands
e-mail: o.p.kuipers[at]rug.nl
tel: (+31) (0) 50 363 2093
fax: (+31) (0) 50 363 2348

 

Partners:

  •  University of Groningen, Netherlands
  • Eberhard Karls University Tübingen (Germany)
  •  Regensburg University (Germany)
  • University College London (United Kingdom)
  •  Organisation for International Dialogue and Conflict Management (IDC) (Austria)
  • ETH Zürich (Switzerland)

 

Project Description:

Synmod (Synthetic biology to obtain novel antibiotics and optimized production systems) proposes to apply a comprehensive synthetic biology approach to the design and production of novel antibiotic molecules. First, evolutionarily pre-determined peptide modules are precisely defined and then re-combined for novel antibiotic functions. The modules are obtained from the group of lantibiotics, post-translationally modified peptide antibiotics. Next, we will assemble a context-insensitive post-translational machinery by exploiting promiscuous modification enzymes and enabling a fine-tuning of the composition of the modification pathway. This will be obtained by organizing the pathway in a modular fashion and providing thoroughly characterized expression elements. This pathway will then be implemented in a novel production chassis of reduced complexity, specifically the Gram-positive Staphylococcus carnosus (2.56 Mg genome), and the resulting strain will be used to manufacture preparative quantities of a variety of novel lantibiotics. By consequently applying the principles of modularity and context-insensitivity on the various levels of the engineering process, we attempt to provide a antibiotic design and production system of unusual robustness and predictability. Using this project as a concrete example, we will analyze the potential impact of synthetic biology on the safety of biotechnological processes and its ethical implications for our society. These considerations will be shared with the public to institute a constructive dialogue about a potentially transformative novel technology.

 
Mode of action of a lantibiotic: Nisin has two modes of action, sequestering lipid 2 stopping cell wall synthesis, the other mode of action is by pore formation causing cell death