Natural secondary metabolites provide an ample source of bioactive compounds with numerous applications, e.g. in the agricultural sector for pest management. Derivatization of their chemical structures is a powerful means to obtain tailored molecules with enhanced or specified bioactivity. The CombiCom FocusLab therefore delivered natural compounds and derivatives to screen for relevant bioactivities. Here, prodiginine tripyrroles were found to suppress phytopathogenic nematode infection and one compound promoted plant growth. Moreover, BioSC activities uncovered nematode inhibiting activities of rhamnolipids, which also show enhanced antibacterial effects when combined with a tripyrrole. In the here proposed TaiLead project we aim to combine these leads. To this end, we will i) establish a microbe-based combinatorial platform for effective production of previously inaccessible new potent tripyrrolic structural variants that are inspired by the plant growth-promoting hit. We will further ii) examine the new compounds regarding their applicability and activity spectrum aspotential agrochemicals. Here, we will assess activities on nematodes and investigate combined activities of prodiginines and rhamnolipids. These analyses will indicate the application range for protection of e.g. sugar beet and soybean against specific parasitic nematodes. Building on key competences of and results obtained by the CombiCom FocusLab, this project thus aims to contribute to the development of sustainable production processes and eco-friendly crop protection solutions.
Bioeconomic relevance: The proposed TaiLead project develops key technologies for the sustainable (bio)synthesis of nature-derived bioactive small molecules in a unique and interdisciplinary approach. Based on potent leads established within the BioSC, new compounds will be combined and their applicability as urgently required next-generation agrochemicals elucidated.
Relevance for the FocusLab: The FocusLab CombiCom operates in the BioSC Focus Topic Area Modular transformations for high-value chemicals. It has the main goal of exploiting natural secondary metabolite pathways and implementing modular concepts to access natural and nature-inspired chemical structures with a bioeconomic value, especially in the agricultural sector. Amongst others, the Junior Groups of A. Loeschcke, T. Classen and S. Schleker have developed essential competences and expertise in the fields of biology, chemistry, and phytopathology. Their conjoint work in the proposed project shall enable lead verification based on compound scaffolds resulting from CombiCom’s screening efforts. Moreover, thus retained expertise will enable future collaborations. Profiling of the BioSC: Thus far, researchers’ efforts have largely focused on other types of compounds, with outstanding achievements e.g. in isoprene and polyketide synthetic biology by Professors Keasling (Berkeley University of California) and Khosla (Stanford University). The prodiginine compounds and respective biosynthetic pathways have also started to attract attention for their diverse bioactivities[1,2], but effects on nematodes and plants, the focus of this proposal, have not been addressed elsewhere. Only recently, a first mutasynthesis approach was demonstrated by competitors, which exploited the substrate flexibility of a monopyrrole-building enzyme, but this approach is not comparable to the technologies and methods established in the applicants’ labs. Therefore, the TaiLead project shall be well perceived (inter)nationally, demonstrating options of fostering a sustainable Bioeconomy based on combinatorial compound synthesis.
Dr. Anita Loeschcke
Institut für Molekulare Enzymtechnologie (IMET)
Heinrich Heine-Universität Düsseldorf
phone: +49 2461 613790
Prof. Jörg Pietruszka, Dr. Thomas Classen, IBOC – Bioorganic Chemistry, HHUD.
Prof. Dr. Florian Grundler, Dr. Sylvia Schleker, INRES – Molecular Phytomedicine, Rhenish Friedrich-Wilhelms University Bonn.
01.08.2020 - 31.10.2021
The total budget of TaiLead is 174,001 €. TaiLead is 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.