Integrating Informatics, Metabolic Engineering and SynBio for the discovery of specialized metabolites
发布时间 :2022-08-11  阅读次数 :4539

Speaker:Tilmann Weber

Professor, Associate Scientific director

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

 

Time:18th August 2022, 15:00-16:00

Tencent  Meeting:360-234-083

Join Tencent Meeting:https://meeting.tencent.com/l/cTWmtwSsgOed

 

Speaker biography:

Tilmann Weber is Professor for Natural Products Genome Mining and Associate Scientific Director of the "Natural Products Genome Mining Group"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. 

Tilmann Weber is member of the Editorial Board Metabolic Engineering, and Associate Editor for Synthetic and Systems Biotechnology. He is coordinator of the NNF-funded Challenge research center “iimena” (2017- 2023) and coordinator of the Horizon Europe MSCA Doctoral Network “MAGic-MOLFUN”. He has published 100+ peer-reviewed papers, with a total citation of 15000+, he is the selectee of the Highly Cited Researchers of 2021.

 

Abstract:

Genome analyses of many microorganisms but also higher organisms 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 whole genome sequences, in silico genome mining has become an indispensable tool to complement the classical chemistry-centered approach to identify and characterize novel secondary / specialized metabolites. Since the initial release in 2011, the open source genome mining pipeline antiSMASH(1) (https://antismash.secondarymetabolites.org), which we develop in collaboration with the group of M. Medema (U. Wageningen, Netherlands) and many international contributors, has become one of the most widely used tools. We are currently working on version 7 of antiSMASH, including the detection of novel BGC families, new visualizations and further improvement. Specialist and non-specialist users can easily analyze genomic sequences for the presence of secondary metabolite biosynthetic gene clusters with antiSMASH.

To provide extensive analysis options of the data generated with antiSMASH, we have extended the framework with several databases (2-4). The antiSMASH database, (https://antismash-db.secondarymetabolites.org/)(2), contains 147,517 high quality BGC regions from 388 archaeal, 25,236 bacterial and 177 fungal “high-quality” genomes.

These genome mining technologies build the foundation of further in silico studies towards a more comprehensive “Genome Analytics” platform, which we use to streamline our natural product discovery and characterization efforts.

Albeit streptomycetes are studied for many decades as proficient producers of bioactive compounds, there are still severe limitations concerning efficiency of mutagenesis protocols that often hamper systems metabolic engineering and Synthetic Biology approaches. We have therefore developed an extensive CRISPR/Cas9-based toolkit (5-8) for streptomycetes that now also includes tools that utilize multiplexing and DSB-free base editing technology to highly effectively engineer actinomycetes

These tools allowed us to identify and characterize various novel BGCs(9-11).