Actinobacteria Metabolic Engineering

The growing resistance towards established antibiotics presents a serious problem especially with infectious diseases. The development of new drugs is mainly based on known molecules and mechanisms, which allows bacteria to assimilate rapidly. Hence, scientists are looking for novel drugs. At the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a site of the Helmholtz Centre for Infection Research (HZI) at Braunschweig, the researchers develop new pathways, by which they force actinomycetes to produce hitherto unknown compounds.

Dr Andriy Luzhetskyy

Head

Dr Andriy Luzhetskyy
Head of Research Group

Our Research

Actinomycetes are a well-known and very intensively examined group of bacteria. They have produced various antibiotics and antitumor drugs and are industrially used to produce antibiotics and agro chemicals. Despite them being thoroughly studied, a huge potential remains still to be revealed. Recent DNA deciphering efforts, where the entire genomes of actinomycetes have been sequenced, revealed that these bacteria remained a very rich source of new potentially active natural products. Hence, a huge reservoir of bioactive molecules stays “hidden” in the numerous publicly available bacterial genomes and metagenomes, confirming the strong limitations of conventional approaches for novel drug discovery. Therefore, the major challenge in the field is exploitation of this untapped genomic potential, and its conversion into bioactive chemical entities for their further development as drugs. In our department we aim to apply a synthetic biology approaches and to develop a truly functional technology platform for discovery, bioengineering and sustainable supply those hidden in genomes compounds for pharmacological testing.

A synthetic biology driven approach includes:

  1. capturing pathways encoding bioactive molecules;
  2. their complete “refactoring” via substitution of every natural regulatory DNA “component” with synthetic genetic control elements;
  3. transplantation of these refactored pathways into simplified reliable bacteria for production of bioactive natural products.

The development of such a generally applicable strategy based on synthetic biology principles of design and construction will enable the discovery of thousands of novel bioactive molecules potentially next efficient drugs.