Synthetic Biology of Rare and Cryptic Cofactors

The Jena School for Microbial Communication (JSMC) is funded by the German Excellence Initiative. JSMC is an ambitious Graduate School with over 150 doctoral researchers who are educated in a structured, interdisciplinary training program based on top-level fundamental research. It conceptually combines different research areas to a comprehensive picture of microbial communication ( Institutes at five facilities of the Friedrich Schiller University Jena, six non-university research institutes as well as 12 partner companies are participating in this cutting-edge research and training program.
The Graduate School of Excellence ‘JSMC’ invites applications for a
Doctoral Researcher Position TV-L E13 65% (Ref. No. HKI 26/2015)
to conduct research on the project

Synthetic Biology of Rare and Cryptic Cofactors

Background: Enzymes catalyze the vast majority of biochemical reactions and thus represent the most complex and versatile functional molecules on earth. In many cases, however, catalysis depends on the presence of small “helper molecules” known as cofactors or prosthetic groups. Therefore, these small molecules are of comparably high importance for biochemical processes. Cofactors are of particular relevance in synthetic biology applications where enzymes are taken out of their natural context to build up artificial metabolic pathways in “universal hosts”. While many cofactors like ATP and FAD are ubiquitous in nature, rare cofactors like cofactor F420 are typically not available in a heterologous host like Escherichia coli. However, rare cofactors might be essential for an enormous number of as-yet underexplored enzymes families with unusual biochemical properties. Going beyond rare cofactors, “hypothetical cofactors” are as-yet undiscovered cofactors that have been postulated by sophisticated genomic analyses. Intriguingly, some of these enigmatic pathways are found in natural product producers or human pathogens. Thus, their discovery and characterization have great potential for biotechnological applications and infection control.
Objectives: Moving towards a “universal host”, rare cofactors will be biosynthesized and made available in this host. Ideally, the production should be regulated and titers fine-tuned according to demand. For cryptic cofactors, the aim will be their identification, structure elucidation and discovery of their biochemical function. Once a novel, engineered host is available, enzymes or entire pathways depending on rare or cryptic cofactors with putative roles in natural product biosynthesis will be expressed in order to obtain novel natural products or biotechnological tools.
Methodology: Cofactor biosynthetic genes will be re-factored by innovative synthetic biology methods. Codons and cis-acting elements will be optimized and regulatory circuits of the host will be introduced. Modern mass spectrometric methods will be employed to monitor cofactor production within the cell. Untargeted metabolomics using high-resolution LC-MS will be performed to identify cryptic cofactors. Finally, candidate metabolites will be purified and subjected to structure elucidation by NMR (through collaboration). Proteomics approaches and targeted gene inactivation experiments will be performed to identify cofactor-dependent enzymes in the natural host. Selected enzymes will be purified as hexahistidine-tag fusion proteins, studied in vitro and made available for crystallographic studies with our collaborators.

  • A Master’s degree (or equivalent) in Life Sciences (e.g. Biology, Biochemistry, Biotechnology or related). Candidates about to earn their degree are welcome to apply.
  • Strong theoretical background in biochemistry, biochemical analytics (e.g. mass spectrometry) , molecular biology and organic chemistry.
  • Practical experience in protein purification and/or proteomics. Hands-on experience in purification and analysis of small metabolites is advantageous. Basic programming skills and an interest in bioinformatics are desirable.
  • High motivation and interest to join one of the interdisciplinary research areas of JSMC
  • Creativity and interest to shape your own thesis project
  • A flexible and cooperative personality with enthusiasm for actively participating in the lively JSMC Community
  • very good communication skills in English (instruction language at JSMC)
We offer:
  • Modern lab equipment including high resolution mass spectrometric devices.
  • Multi-disciplinary environment
  • A highly communicative atmosphere within a scientific network providing top-level research facilities
  • A doctoral researcher position (TV-L E13, 65%) with guaranteed funding for one and a half years based on the regulations of the German Research Foundation as well as generous research funding with the possibility of funding extension for completion of the PhD project
  • A comprehensive mentoring program with supervision by a team of advisors
  • A top-level PhD training program with courses in state-of-the-art research technologies and soft skills
  • Jena – City of Science: a young and lively town with dynamic business activities, successful scientific centers of innovation and a vibrant cultural scene around the famous Friedrich Schiller University
Friedrich Schiller University Jena is an equal opportunity employer. Disabled persons with comparable qualifications receive preferential status.

The application procedure takes place exclusively online via the JSMC website:

Please acquaint yourself with the open PhD projects and the application process described on this website.

Selected applicants will be invited to the JSMC Recruitment Meeting in Jena, Germany, in January 2016. Awarding decisions will be made shortly thereafter, allowing the projects to start immediately.

Application deadline: November 17th, 2015
How to apply:
The application procedure takes place exclusively online via the JSMC website:
Please acquaint yourself with the open PhD projects and the application process described on this website.
Send application to
While applying for the job please refer to jobvector and use the following reference number: Ref. No. HKI 26/2015

About Jena School for Microbial Communication

The Jena School for Microbial Communication (JSMC) is funded by the German Excellence Initiative . It conceptionally combines different research areas (microbial communities, interactions with plant, animal and human hosts and environmental interactions) to a comprehensive picture of microbial communication ( JSMC is an ambitious Graduate School currently hosting over...

More about Jena School for Microbial Communication

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