Tilmann Weber

@tilmweber.bsky.social

Professor at DTU NNF Center for Biosustainability with interest in bioactive compounds, comp. biol., WGS and much more; hobby photographer. Views are my own.

The MIBiG 5.0 Annotathon is coming soon, and registration is now open! 🧬 Does your research involve biosynthetic gene clusters? Do you love natural product biosynthesis? Do you have an interest in rare & exotic enzymes? We can use your help & expertise. Register here 👉 forms.gle/C1cWcLHtrjT2...

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New paper alert!! Led by Lucas, we automated all the design steps for genome engineering experiments in streptomycetes. If you are using our Streptomyces CRISPR toolbox, you can now design hundreds of experiments in a matter of minutes. @tilmweber.bsky.social @kblin.bsky.social ....

StreptoCAD: An Open-Source Software Toolbox Automating Genome Engineering Workflows in Streptomycetes

Streptomycetes hold immense potential for discovering novel bioactive molecules for applications in medicine or sustainable agriculture. However, high-throughput exploration is hampered by the current Streptomyces genetic engineering methods that involve the manual design of complex experimental molecular biological engineering strategies for each targeted gene. Here, we introduce StreptoCAD, an open-source software toolbox that automates and streamlines the design of genome engineering strategies in Streptomyces, supporting various CRISPR-based and gene overexpression methods. Once initiated, StreptoCAD designs all necessary DNA primers and CRISPR guide sequences, simulates plasmid assemblies (cloning) and the resulting modification of the genomic target(s), and further summarizes the information needed for laboratory implementation and documentation. StreptoCAD currently offers six design workflows, including the construction of overexpression libraries, base-editing, including multiplexed CRISPR-BEST plasmid generation, and genome engineering using CRISPR-Cas9, CRISPR-Cas3, and CRISPRi systems. In addition to automating the design process, StreptoCAD further secures compliance with the FAIR principles, ensuring reproducibility and ease of data management via standardized output files. To experimentally demonstrate the design process and output of StreptoCAD, we designed and constructed a series of gene overexpression strains, and performed CRISPRi knockdowns in Streptomyces Gö40/10, underscoring the tool’s efficiency and user-friendliness.. This tool simplifies complex genetic engineering tasks and promotes collaboration through standardized workflows and design parameters. StreptoCAD is set to transform genome engineering in Streptomyces, making sophisticated genetic manipulations accessible for all and accelerating natural product discovery.

pubs.acs.org

𝘚𝘵𝘳𝘦𝘱𝘵𝘰𝘮𝘺𝘤𝘦𝘴 (and 𝘒𝘪𝘵𝘢𝘴𝘢𝘵𝘰𝘴𝘱𝘰𝘳𝘢🙂) aficionadas y aficionados take note 👇 ...and no, the image doesn't show reconstituted 𝘒𝘪𝘵𝘢𝘴𝘢𝘵𝘰𝘴𝘱𝘰𝘳𝘢 telomeres (telomores) 😉 #MicroSky

image from https://alchetron.com/Kitasatospora
Tue Sparholt Jørgensen@tuesparholt.bsky.social · 10mo ago

Bacterial telomeres are common, just not so much in RefSeq 'complete' genomes. But they can be added by the new tool David Faurdal wrote. I am thrilled to see this out as a preprint here: www.biorxiv.org/content/10.1... @tilmweber.bsky.social @thombooth.bsky.social

Be sure to read this review, part of our Industrial Perspective themed collection, by Stefano Donadio & co. from NAICONS Srl discussing the trends in metabolite discovery from Actinomycetes #secmet #natprod Find it in full below👇

Trends in metabolite discovery from Actinomycetes

Covering: 2013 to 2023 In this review, we analyzed the scientific literature of the period 2013–2023 that reported novel specialized metabolites from the Actinomycetes, one of the most prolific…

pubs.rsc.org

A key aspect of my @erc.europa.eu Advanced project 'Community' was to predict biosynthetic gene cluster (BGC) function entirely on how BGCs are controlled, without looking at predicted gene function or natural product. We show proof of concept for this idea in this paper in @plosbiology.org (1/2)

PLOS Biology@plosbiology.org · last yr.

Most #biosynthetic gene clusters remain uncharacterized. @marnixmedema.bsky.social @gillesvanwezel.bsky.social &co integrate #GRN analysis & global expression data to identify desJGH as an operon essential for #biosynthesis of #desferrioxamineB in Streptomyces @plosbiology.org 🧪 plos.io/43UVUPB

Left: Predicted gene regulatory network of Streptomyces coelicolor based on 17 well-known regulators. Each node in the network represents a (regulatory) gene, and every edge represents a PWM predicted regulatory interaction between nodes. The edges colored in dark gray indicate strong PWM prediction scores, while the lighter gray shades represent weaker interactions. Matches within BGC regions are depicted as triangles. In six regions (black circled), the matches fall within a co-expressed region, highlighting their functional relation to these compounds. Right: Proposed biosynthetic pathway for assembly of desferrioxamines E and B. Main biosynthetic enzymes presented in bold face. DesG and DesH balance intracellular N-hydroxy-N-succinylcadaverine (HSC) and N-hydroxy-N-acetylcadaverine (HAC) concentrations by converting HSC to HAC. In the absence of DesG and/or DesH, the cells likely fail to produce sufficient levels of HAC, thereby strongly attenuating the production of DFOB. Although DesC has been shown to be able to catalyze the acetylation of N-hydroxycadaverine in vitro, the enzyme can only modestly compensate for the loss of DesH in vivo, underlining the important role played by DesG and DesH in DFOB production.

We’ve just released #antiSMASH 8.0.1, a bug-fix release. Find the tarball and containers in the usual places, it’s also live on our website now. Bioconda containers aren’t built by us, they might take a while to update. We recommend installing deps via bioconda and then running from our releases.

I can highly recommend you to try out this tool developed by my PhD student @andersohd.bsky.social and other members of our research group in collaboration with @tilmweber.bsky.social team. It is still a beta version, but we hope to finish it soon.

Freya Harrison@friendlymicrobe.bsky.social · last yr.

Now at #Biofilms11, @andersohd.bsky.social is introducing epssmash.secondarymetabolites.org - a tool for mining microbial genomes for exopolysaccharide biosynthetic gene clusters. Looks really valuable for finding new & different #biofilm producers #MicroSky

I am thrilled to share after years of work/procrastination that the MassQL manuscript is finally published in @natmethods.nature.com - "A universal language for finding mass spectrometry data patterns". This was an team effort from all co-authors that helped shape MassQL and how it could be used.