Natural products represent an invaluable source of bioactive compounds. They can serve as chemical frameworks for developing new agrochemicals and pharmaceuticals that are urgently needed to meet the growing demands of modern society. Reinforcing the change of paradigm from synthetic chemistry to sustainable microbial production, CombiCom will thus exploit secondary metabolite pathways to deliver natural compounds and further extend these structures by exploring the non-natural chemical space beyond. We will pursue an integrated approach by joining forces of experts in biology, chemistry and engineering to create synthetic biology-tailored microbial chassis allowing for the sustainable production of novel high-value compounds, which will be evaluated for their anti-phytopathogenic activity and pharmaceutical potential. This endeavor will be accompanied by the assessment of related socioeconomic implications, aiming to evaluate and optimize the market introduction potential of synthetic biology associated products.
Aiming to reinforce the change of paradigm from synthetic chemistry to sustainable microbial production, key technologies for the sustainable (bio)synthesis of natural and nature-inspired compounds will be developed in a unique and interdisciplinary approach. Inspired by the modular architecture of natural biosynthetic pathways, engineering concepts will be implemented on different pathways, specifically exploiting the joined expertise of CombiCom partners in the fields of biology, chemistry, and engineering.
Biological phyto-protection activities of the new compounds will be evaluated, targeting relevant pathogens of the crop plant rapeseed which represents an important part of the local agricultural landscape. The FocusLab thus aims to promote novel, sustainable, and resource-efficient crop protection strategies. Moreover, CombiCom will specifically address socioeconomic aspects of market introduction of synthetic biology-derived products. Thereby, the dialogue with society and important stakeholders is fostered to ultimately strengthen the acceptance of synthetic biology for a sustainable bioeconomy.
Dr. Anita Loeschcke
Institute of Molecular Enzyme Technology of the Heinrich-Heine-University Düsseldorf
located at Forschungszentrum Jülich, Geb. 15.8
01.05.2017 – 30.04.2020
The total budget of CombiCom is € 2.392.370. CombiCom is part of the NRW-Strategieprojekt BioSC and thus funded by the Ministry of Culture and Science of the German State of North Rhine-Westphalia.
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Hage-Hülsmann J, Grünberger A, Thies S, Santiago-Schübel B, Klein AS, Pietruszka J, Binder D, Hilgers F, Domröse A, Drepper T, Kohlheyer D, Jaeger K-E, Loeschcke A (2018). Natural biocide cocktails: Combinatorial antibiotic effects of prodigiosin and biosurfactants. PLoS ONE 13(7): e0200940.
Klein AS, Brass HUC, Klebl DP, Classen T, Loeschcke A, Drepper T, Sievers S, Jaeger K-E, Pietruszka J (2018). Preparation of cyclic prodiginines by mutasynthesis in Pseudomonas putida KT2440. ChemBioChem 19(14): 1545-1552.
Chatelle C, Ochoa-Fernandez R, Engesser R, Schneider N, Beyer HM, Jones AR, Timmer J, Zurbriggen MD, Weber W (2018). A Green-Light-Responsive System for the Control of Transgene Expression in Mammalian and Plant Cells. ACS Synthetic Biology 7(5):1349-1358.
Loeschcke A, Dienst D, Wewer V, Hage-Hülsmann J, Dietsch M, Kranz-Finger S, Huren V, Metzger S, Urlacher VB, Gigolashvili T, Kopriva S, Axmann IM, Drepper T and Jaeger K-E (2017). The photosynthetic bacteria Rhodobacter capsulatus and Synechocystis sp. PCC 6803 as new hosts for cyclic plant triterpene biosynthesis. PLoS One 12(12): e0189816.
Klein AS, Domröse A, Bongen P, Brass HUC, Classen T, Loeschcke A, Drepper T, Laraia L, Sievers S, Jaeger KE, Pietruszka J (2017). New Prodigiosin Derivatives Obtained by Mutasynthesis in Pseudomonas putida. ACS Synthetic Biology6(9): 1757–1765.
Domröse A, Weihmann R, Thies S, Jaeger K-E, Drepper T and Loeschcke A (2017). Rapid generation of recombinant Pseudomonas putida secondary metabolite producers using yTREX. Synthetic and Systems Biotechnology 2(4): 310-319.