SYSTERACT: Systematic Rebuilding of Actinomycetes for Natural Product Formation

SYSTERACT: Systematic Rebuilding of Actinomycetes for Natural Product Formation

The main objective of the SYSTERACT project is through an integrated and interdisciplinary approach to develop the model actinomycete Streptomyces coelicolor into a "Superhost" for the efficient heterologous production of bioactive compounds, enabling a faster discovery of new antibiotics from environmental microbial resources (microbial strains and metagenomes). Central to this approach will be an iterative Systems Biology process, combining microbiology, genetics, biochemistry, and fermentation technology with modelling.

There is an urgent need for novel antibiotics to fight life-threatening infections and to counteract the increasing problem of propagating antibiotic resistance. Despite this increasing medical need, the number of new antibiotics approved for human use has been declining over the many years. Recently, new molecular genetic and biochemical tools, and in particular Next Generation Sequencing combined with newly developed bioinformatics approaches, have provided insight into the enormous unexploited genetic pool of environmental microbial biodiversities for the synthesis of potential new bioactive compounds. However, a limiting issue for a new antibiotic is how fast and effectively it can be developed and brought to the market. Addressing this issue with efficient tools for new antibiotic discovery and production is critical for the competitiveness of European industry as well as for a cost-saving medical service for European citizens.

SYSTERACT brings together six partners from four ERA-SysApp member countries, including four universities, one non-profit research organization, as well as the latter's Technology Transfer Unit. An advisor from the United Kingdom will contribute to the project with his high expertise in the field of actinomycete physiology. Crucial biological strain material has already been obtained from the partners' contacts at the John Innes Centre (JIC) in Norwich, UK. Strong relevant industry is closely connected to the project (Letters of Interest of Evonik (D), Xellia Pharmaceuticals (NO), and BaseClear (NL) are included in this application). The project will build on and utilize the comprehensive expertise, data and models acquired in the ERA-Net SysMO project STREAM, as well as existing Streptomyces coelicolor strains generated at JIC, on its way to optimized "Superhost" strains for heterologous antibiotics production.

Related publications

Enzyme-constrained models and omics analysis of Streptomyces coelicolor reveal metabolic changes that enhance heterologous production

Sulheim S, Kumelj T, van Dissel D, Salehzadeh-Yazdi A, Du Ch, P. van Wezel G, Nieselt K, Almaas E, Wentzel A, Kerkhoven E

Applications of genome-scale metabolic models and data integration in systems medicine

Salehzadeh-Yazdi A, Wolfien M, Wolkenhauer O

Nova (2019), chapter in Focus on Systems Theory Research

ISBN 13 (online): 9781536145618