第494次SKLBE学术论坛（丹麦科技大学 Tilmann Weber 教授）

题目：In silico and in vitro approaches to analyze the biosynthesis of microbial specialized metabolites

报告人： 丹麦科技大学 Tilmann Weber 教授

时间：   2019-11-20（周三）15:00-

地点：   实验18楼315室

主持人：  张立新教授

  Tilmann Weber is Professor and Co-Principal Investigator for Natural Products Genome Mining at the Novo Nordisk Foundation Center for Biosustainability of the Technical University of Denmark. His main research interest is focused on deciphering the molecular pathways and engineering the biosynthesis of natural products by combining genetic, biochemical and bioinformatics methods. He is a pioneer in developing software for the automated genome mining (CLUSEAN, antiSMASH, antiSMASH-DB) and analysis of secondary metabolite biosynthetic pathways. His group was able to firstly elucidate the biosynthetic pathways of the elfamycin family of antibiotics and is deeply involved in developing CRISPR-based metabolic engineering tools for actinomycetes.

In silico and in vitro approaches to analyze the biosynthesis of microbial specialized metabolites

Genome analyses of many microorganisms indicate that the genetic potential to synthesize specialized metabolites is far beyond the number of molecules observed in traditional screenings. With the availability of cheap and easy-to-obtain microbial whole genome sequences, in silico genome mining has become an indispensable tool to complement the classical chemistry-centred approach to identify and characterize novel secondary / specialized metabolites. Since the initial release in 2011, the open source genome mining pipeline antiSMASH (https://antismash.secondarymetabolites.org) has become one of the most widely used tool to provide such analyses to the scientific public. We recently released version 5 of antiSMASH¹, including an improved user interface, new detection modules and many internal optimizations. With antiSMASH users can easily analyze genomic sequences for the presence of secondary metabolite biosynthetic gene clusters. To provide extensive analysis options of the data generated with antiSMASH, we have added the antiSMASH database² (https://antismash-db.secondarymetabolites.org/) to the antiSMASH-framework, a user-friendly application allowing to browse and query antiSMASH annotation of >6,000 high-quality and >18,000 bacterial genomes as well as the new MIBiG v2 database³ containing manually validated and curated BGC information.

These genome mining technologies build the foundations of our experimental work on actinomycetes. Albeit studied for many decades, there are still severe limitations concerning efficiency of mutagenesis protocols that often hamper systems metabolic engineering and Synthetic Biology approaches. We have developed an extensive CRISPR/Cas9-based toolkit for streptomycetes^3,4 that now also includes tools that utilize DSB-free base editing technology to highly effectively engineer actinomycetes.

References

¹Blin, K., et al., 2019, Nucleic Acids Res. 47:W81-W87

²Blin, K., et al., 2019, Nucleic Acids Res. 47:D625-D630

³Kautsar, S. A., et al., 2019, Nucleic Acids Res., https://doi.org/10.1093/nar/gkz882

⁴Tong, Y., et al., 2015, ACS Synth. Biol. 4:1020-9

⁵Tong, Y., et al., 2019, Proc. Natl. Acad. Sci. U. S. A. 116:20366-20375