Graduate School MINAS

  TU Brauschweig Institut für Organische Chemie      


Participating groups

» Area A: Synthesis
» Area B: Biosynthesis, isolation and production
» Area C: Biological activity and biological response


Project area B: Biosynthesis, isolation, and production
Project B1: Systems Metabolic Engineering of Escherichia coli for the Biosynthesis of Natural Products
Prof. Dieter Jahn, Institute of Microbiology, TU Braunschweig
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Prof. Rainer Krull, Institute of Biochemical Engineering, TU Braunschweig
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The project aims at rational design and engineering of E. coli strains into recombinant tailor-made cell factories for natural products derived from tryoptphane. Exemplified for violacein, deoxyviolacein and rebeccamycin it will integrate cultivation and bioanalytics with novel concepts from systems and synthetic biology. Currently, these valuable compounds are difficult to provide due to low product levels, weak growth and inaccessible genetics of their natural producers, suggesting well-known E. coli as most promising candidate for production.
Required qualification: Master in Biotechnology, Chemistry, Biology, Molecular Biology or similar

Project B2: Isolation and Characterization of Antimicrobial Compounds Produced by Paenibacillus larvae
Prof. Michael Steinert, TU Braunschweig, Institut für Mikrobiologie
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The Gram-positive, spore-forming bacterium Paenibacillus larvae is the causative agent of American Foulbrood (AFB), a fatal disease of honeybee larvae. Through the production of antimicrobial compounds P. larvae out competes the larval microflora and can be isolated as pure culture from infected dead larvae. Extracted compounds from P. larvae culture medium exhibit strong antagonistic activities against numerous tested Gram-positive and Gram-negative bacteria and are the starting material for further purification, identification and characterization. The final aims of the project are to develop potential therapeutic lead structures against antibiotic-resistant bacteria und to better understand the pathogenicity of the most deleterious bacterial disease of honeybees.
Required qualification: Master in Biology, Biochemistry or Chemistry

Project B3: Biosynthesis, production and mode of action of unusual fatty acid derived antibiotics form myxobacteria
Prof. Rolf Müller, HZI Braunschweig, Mikrobielle Wirkstoffe
Web address:
Unusual fatty acid derivatives are novel antibiotics from myxobacteria exhibiting a pharmaceutically promising spectrum of activity against gram-negative bacteria. In this project we aim to identify the biosynthetic gene cluster, improve production and elucidate the mode of action of these compounds. Once the biosynthesis is understood, heterologous expression and biosynthetic engineering will be used to generate modified compounds to improve pharmaceutical properties and activity. Derivatives will be used for activity assays and possibly also medicinal chemistry approaches in collaboration with the Schulz group.

Required qualification: Master in Chemistry, Biology, Biotechnology or Pharmacy

Project B4: Using Bacterial Biosynthetic Machineries for the Production of Functional Molecules
Dr. Jeroen Dickschat, TU Braunschweig, Institut für Organische Chemie
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Terpenes, polyketides, and non-ribosomal peptides make up important classes of natural products with interesting bioactivities including antibiotic or cytotoxic properties. In some cases the biosynthetic pathways to such molecules show a high flexibility, thus allowing for the successful feeding of alternative building blocks such as fluorinated compounds to bacterial cultures. Alternatively, building blocks with a photoactivatable functional group can be fed. The efficiency of incorporation can significantly be increased by genetic engineering of the respective biosynthetic pathway. In an alternative approach key enzymes that are involved in the biosynthesis of a complex natural product may be heterologously expressed and purified. The enzyme can then be used for the in vitro conversion of fluorinated or photoactivatable precursors. The applicant will be involved in compound feeding, purification and structure elucidation of the obtained "non-natural" natural products, testing of their (antibiotic) properties, and genetic pathway engineering. The fluorinated and photoactivatable precursors will be synthesized and provided by in-house collaboration partners (A6 - Prof. Lindel, A1 - Prof. Schulz).
Required qualification: Master in Chemistry, Biotechnology, Biology or similar

Project B5: Enzymology of isolated functional domains from iterative Fungal Polyketide Synthases
Professor Russell Cox, Leibniz University Hannover, Institute of Organic Chemistry Dr. Frank Hahn, Leibniz University Hannover, Institute of Organic Chemistry
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Fungal polyketide synthases (PKS) are remarkable enzymes which iteratively use a small number of carbon-carbon bond-forming and modifying enzyme domains to create complex, often biologically active, small molecules. Fungal PKS are programmed so that in each round of extension and modification the growing chain can undergo different chemistry. In order to understand the root of this cryptic programming this project will investigate the selectivities of individual isolated enzyme domains using synthetic substrates. The project will involve the use of molecular biology and protein expression to obtain the functional fragments of a fungal PKS, synthetic chemistry to make substrates in enantiomerically pure (and often isotopically labelled) forms and detailed analytical chemistry and enzymology. Interested candidates should have experience in synthetic chemistry and natural products chemistry.
Required qualification: Master in Chemistry