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MAtching Genes with MOLecules for FUNctional Analysis

Periodic Reporting for period 1 - MAGic-MOLFUN (MAtching Genes with MOLecules for FUNctional Analysis)

Reporting period: 2023-01-01 to 2024-12-31

The MAGIC-MOLFUN doctorial network (DN) will train the next generation of specialists for transforming natural products research. They will be educated in a combination of wet-lab and computational skills to integrate genome mining and metabolomics with cutting-edge pathway discovery- and engineering approaches. There is a fast-growing demand for these combination of skills, but these are rarely taught in current integrated training programs. These multidisciplinary skills and qualifications will be acquired while achieving the scientific goals of the program, namely understanding and developing the complex biosynthesis and production of microbial NPs for cross-sector applications such as medicine, food, agriculture, or biotechnology.

Within the research program, 3 research objectives (RO) will be addressed.
We will (i) develop novel computational tools and algorithm to improve the identification and prediction quality of biosynthetic gene clusters in genomic data. Furthermore, (ii) we will use cheminformatics approaches to link metabolomics data of NPs with the genomic data of the producers, which will greatly improve the compound discovery and dereplication process. These two approaches will finally (iii) converge to be applied to find and characterize novel bioactives (antibiotics, pre-/probiotics, agrichemicals, bio-pigments) in bacteria and fungi.

The scientific training program is complemented by a comprehensive transferable skill training that will equip the DCs for todays’ demands of a successful career in industry and academia. The skills obtained in the DN will enable the DCs to work not only in natural product research but also many other data-intensive areas of biotechnology.
All the DCs have started their individual research projects and attended the kick-off meeting at DTU in Denmark and the first “Advanced Scientific Course (ASC1) 1” on “Specialized metabolite Genome Mining” at Wageningen University in the Netherlands, ASC2 on "Natural Products (Bio)Chemistry and Metabolomics", together with the DN HOTBIO at Fundación MEDINA in Spain, ASC3 on "Metabolic Engineering of NP producers" at University Tübingen in Germany. Furthermore they were offered various online/on-site transferable skill courses (TSC1-3) on Scientific Networking and good scientific practices, Scientific communication and Scientific writing. All DCs attended a workshop (TSC4) on Equality in Science.

While the research projects are still running, several DCs already contributed to a new “Minimum Information on Tailoring Enzymes (MITE)” standard proposal, which was published as a ChemRxiv preprint (Zdouc, M. M., et al., 2024, ChemRxiv DOI: 10.26434/chemrxiv-2024-78mtl) the latest release of the MIBiG "Minimum Information on Biosynthetic Gene Clusters" standard and repository and the upcoming antiSMASH version 8.
All research projects of the DCs are centered around the idea, to improve our predictive capabilities in Natural Products research, both from the genomics and metabolomics angle and therefore are expected to make an significant impact on the whole field.
MAGic-MOLFUN significantly contributed to several large community-driven projects, such as the latest release of the MIBIG standard and repository (version 4; publication in NAR), the new MITE standard and repository (ChemRxiv preprint) and several DCs contributed new functionalities to the gold-standard genome mining software antiSMASH (beta version of antiSMASH 8 released).
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