Prof Dr Andriy Luzhetskyy
Actinomycetes are a well known and very intensively studied group of bacteria. They have produced various antibiotics and antitumor agents and are used industrially to produce antibiotics and agrochemicals. Although they have been thoroughly studied, a huge potential remains to be discovered. Recent DNA decoding work, in which the entire genomes of actinomycetes have been sequenced, has shown that these bacteria remain a very rich source of new potentially active natural products. Thus, a vast reservoir of bioactive molecules remains "hidden" in the numerous publicly available bacterial genomes and metagenomes, confirming the severe limitations of conventional approaches to new drug discovery. The major challenge in this field is therefore to exploit this untapped genomic potential and transform it into bioactive chemical entities for further development as drugs. The Luzhetskyy group aims to apply a synthetic biology approach and develop a truly functional technology platform for the discovery, bioengineering, and sustainable delivery of compounds hidden in genomes for pharmacological testing.
A synthetic biology-based approach involves:
1. capturing metabolic pathways that encode bioactive molecules;
2. completely "remodeling" them by replacing all natural regulatory DNA "components" with synthetic genetic control elements;
3. the transplantation of these remodeled metabolic pathways into simplified, reliable bacteria for the production of bioactive natural products.
The development of such a generally applicable strategy based on the design and engineering principles of synthetic biology will enable the discovery of thousands of novel bioactive molecules that may be the next effective drugs.