Simon Sieber

Simon Sieber

@simonsieber.bsky.social

PI at the University of Zürich. Natural Products Discovery, Metabolomics, Bacteria Metabolites, Cyanobacteria Blooms, Quorum Sensing, Chemoselective Probes, Diazeniumdiolates. https://www.simonsiebergroup.com/

950 followers1.1K following14 posts

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Simon Sieber
@simonsieber.bsky.social

Our highlight review on recently isolated cyanobacterial metabolites is out @natprodreports.rsc.org !🥳 Covers isolation, structure elucidation (analytical techniques, biosynthesis and total synthesis). Great work with @elisabethjanssen.bsky.social! @chem.uzh.ch pubs.rsc.org/en/content/a...

pubs.rsc.orgHighlights of cyanobacterial metabolites reported between 2021–2024Covering: 2021 to 2024This review highlights cyanobacteria secondary metabolites reported between 2021 and 2024. Those compounds are categorised into major classes, including peptides, alkaloids, lipi...

Simon Sieber reposted

Mitja M. Zdouc
@mmzdouc.bsky.social

Aaand it's out! Meet MITE - the natural product tailoring enzyme database, just published in @narjournal.bsky.social! MITE DB captures the substrate- and reaction-specificity of tailoring enzymes, allowing to capture this information in a human- and machine-readable way! doi.org/10.1093/nar/...

doi.orgMITE: the Minimum Information about a Tailoring Enzyme database for capturing specialized metabolite biosynthesisAbstract. Secondary or specialized metabolites show extraordinary structural diversity and potent biological activities relevant for clinical and industria
Mitja M. Zdouc@mmzdouc.bsky.social

Into natural product biosynthesis & tailoring enzymes? Frustrated by the lack of a dedicated resource to explore their functions? Tired of endless literature searches for reaction info? Meet the MITE database, freely available at mite.bioinformatics.nl. Preprint: doi.org/10.26434/che... (1/8)

Simon Sieber
@simonsieber.bsky.social

Thrilled to see our study on novel toxins from cyanobacteria blooms in #Fribourg in STOTEN! Our results indicate that Phormidium is the producer of cyanopeptolins, whose side chains are crucial for their activity. Great collaboration with Pilar Junier www.sciencedirect.com/science/arti...

sciencedirect.comGenomic and chemical characterization of cytotoxic Ahp-cyclodepsipeptides from Phormidium using Thamnocephalus platyurus bioassayToxic benthic cyanobacterial mats have been identified globally as a potential health hazard since they can produce potent cyanotoxins. Such mats have…

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Erika Martínez
@eri-bemr.bsky.social

Thanks to the organisers for a fantastic #ICTC13 and to all the participants for the super fruitful discussions. It was my first ICTC and I had such a wonderful experience 🤩. I'm so looking forward to ICTC14 👀 @ictc13.bsky.social

ICTC13@ictc13.bsky.social

Our group photo ❤️. Big thanks to all participants for their contributions.

Simon Sieber reposted

Tobias Schnitzer – Group Leader @ Uni Freiburg
@schnitzerlab.bsky.social

🎉 Big day for our group: our first publication is out! Tom did a fantastic job highlighting current trends & opportunities in peptide catalysis — now published in Chem Catalysis (open access). Huge congrats, Tom! www.cell.com/chem-catalys...

cell.comPeptide catalysis: Trends and opportunitiesPeptides are highly selective organocatalysts, with intrinsic modularity allowing precise control over structure and function. Advances in peptide synthesis, biotechnology, and cheminformatics will en...

Simon Sieber reposted

Sieber Lab
@sieberlab.bsky.social

Excited to share our new preprint: AI-guided Antibiotic Discovery Pipeline from Target Selection to Compound Identification! It includes a comprehensive benchmark of structure-based drug design (SBDD) methods and presents a full, practical pipeline for antibiotic discovery. arxiv.org/abs/2504.11091

arxiv.orgAI-guided Antibiotic Discovery Pipeline from Target Selection to Compound IdentificationAntibiotic resistance presents a growing global health crisis, demanding new therapeutic strategies that target novel bacterial mechanisms. Recent advances in protein structure prediction and machine ...

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Fundación MEDINA
@medinadiscovery.bsky.social

A new research article from @medinadiscovery.bsky.social is now out in Journal of Natural Products. It describes the discovery of a novel family of isocyanide antibiotics with broad spectrum activity against Gram negative bacteria. pubs.acs.org/doi/10.1021/...

pubs.acs.orgMDN-0057 to MDN-0060, a Family of Broad-Spectrum Antibiotics against Gram-Negative Pathogens Produced by Ophiosphaerella korraeA novel family of antibiotics, MDN-0057 to MDN-0060 (1–4), was isolated from liquid cultures of the fungus Ophiosphaerella korrae. These compounds incorporate two isocyanide groups in their complex structures that were elucidated by extensive spectroscopic analyses, including HRESIMS, and 1D and 2D NMR experiments. The relative configurations were determined by using J-based configuration analyses and the interpretation of key NOESY correlations consistent with the existence of a major conformation in solution. Mosher ester derivatization analysis allowed the establishment of their absolute configurations. All four compounds displayed in vitro antibacterial activity with a broad spectrum against Gram-negative pathogens.

Simon Sieber reposted

Brian O. Bachmann
@brianobachmann.bsky.social

We put together this protocol in part to encourage broader adoption of Multiplexed Activity Metabolomics, an engine for functional metabolomics of all types including specialized metabolite discovery. We enjoy knowing if metabolite is active before isolating it, and so should you! #natprod

sciencedirect.comMultiplexed cytometry for single cell chemical biologyFlow cytometry has great potential for screening in translational research areas due to its deep quantification of cellular features, ability to colle…

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Gerry Wright
@gdwantibiotics.bsky.social

The latest discovery from the lab and great colleagues at McMaster and U Illinois, Chicago. Lariocidin, a new lasso peptide antibiotic that inhibits the ribosome. rdcu.be/efdha

rdcu.beA broad-spectrum lasso peptide antibiotic targeting the bacterial ribosomeNature - A new lasso peptide antibiotic exhibits broad-spectrum activity against Gram-negative and Gram-positive bacteria by interfering with bacterial protein synthesis, is unaffected by common...

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Antimicrobial resistance #AMR
@antimicrobial.bsky.social

The newly discovered lariocidine has shown promise against AMR bacteria by targeting ribosomes with a novel mechanism of action. While still years away from market approval, its potential to combat #AMR infections offers hope in addressing the global AMR crisis. www.thevermilion.com/why-could-a-...

thevermilion.comWhy could a new class of antibiotics really make a difference?The discovery of penicillin dates back to 1928. And since then, antibiotics have contributed to saving millions of lives all over the world, extending the average duration of human life by 23 years. I...

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BioMassSpec
@realbiomassspec.bsky.social

Dereplication of secondary metabolites from Sophora flavescens using an LC–MS/MS-based molecular networking strategy #SciRep www.nature.com/articles/s41...

nature.comDereplication of secondary metabolites from Sophora flavescens using an LC–MS/MS-based molecular networking strategy - Scientific ReportsScientific Reports - Dereplication of secondary metabolites from Sophora flavescens using an LC–MS/MS-based molecular networking strategy

Simon Sieber reposted

Mingxun Wang
@mingxunwang.bsky.social

I am excited to share this new paper out in JPR - "MS-RT: A Method for Evaluating MS/MS Clustering Performance for Metabolomics Data." This work introduces the MS-RT method to assess MS/MS clustering accuracy on metabolomics data. doi.org/10.1021/acs....

doi.orgMS-RT: A Method for Evaluating MS/MS Clustering Performance for Metabolomics DataThe clustering of tandem mass spectra (MS/MS) is a crucial computational step to deduplicate repeated acquisitions in data-dependent experiments. This technique is essential in untargeted metabolomics, particularly with high-throughput mass spectrometers capable of generating hundreds of MS/MS spectra per second. Despite advancements in MS/MS clustering algorithms in proteomics, their performance in metabolomics has not been extensively evaluated due to the lack of database search tools with false discovery rate control for molecule identification. To bridge this gap, this study introduces the MS1-retention time (MS-RT) method to assess MS/MS clustering performance in metabolomics data sets. Here, we validate MS-RT by comparing MS-RT to established proteomics clustering evaluation approaches that utilize database search identifications. Additionally, we evaluate the performance of several MS/MS clustering tools on metabolomics data sets, highlighting their advantages and drawbacks. This MS-RT method and the MS/MS clustering tool benchmarking will provide valuable real world practical recommendations for tools and set the stage for future advancements in metabolomics MS/MS clustering.

Simon Sieber reposted

Dirk Trauner
@dirktrauner.bsky.social

Dearomative Diels-Alder reactions are currently hot in total synthesis. They go back to Peter Yates (who trained my mentor Sam Danishefsky). And the Wessely reaction was also discovered in Vienna :)

Simon Sieber reposted

Tri Kaloudis
@trikaloudis.bsky.social

Two very nice applications of molecular networking published this week. One for natural compounds doi.org/10.1021/jacs... and one for #PFAS doi.org/10.1038/s414... @gnps2.bsky.social #teammassspec

doi.orgA Systematic Approach to Discover New Natural Product Scaffolds Using Database-Derived Relative Mass Spectral Defects and Molecular NetworkingRapid advances in mass spectrometry (MS) data analysis have accelerated the identification of natural products from complex mixtures such as natural product extracts. However, limitations in MS data in metabolite libraries and dereplication strategies are still lacking for assigning structures to known compounds and searching for unidentified compounds. To overcome these limitations, we present an approach that combines molecular networking with MS database-derived mass defect analysis to preferentially discover new compounds with high structural novelty in the initial stage of a discovery workflow. Specifically, unknown metabolites or clusters generated from molecular networking are assigned to a compound class based on their relative mass defects (RMDs) calculated using open-source databases. If ancillary data such as ultraviolet and MS/MS spectra of the unknown clusters are incongruent with the RMD-assigned compound class, metabolites are considered to have a new skeleton that exhibits a large difference in RMD value due to structural changes. Here, we applied this RMD-assisted method to a desert-derived bacterial strain library and validated it through the discovery of brasiliencin A (1), a new 18-membered macrolide from Nocardia brasiliensis. A putative biosynthetic pathway of brasiliencin A was proposed through whole-genome sequence analysis, and an additional 29 analogs were detected using absolute mass defect filtering (AMDF) based on plausible biosynthetic products. This led to the isolation of three additional macrolides, brasiliencins B–D (2–4). The structures of the brasiliencins (1–4) were fully elucidated through spectroscopic data analysis and quantum chemical calculations including ROE distance and 13C NMR chemical shift calculations, and experimental and theoretical electronic circular dichroism (ECD). Brasiliencin A showed strong activity against Mycobacterium smegmatis and Streptococcus australis (MIC = 31.3 nM and 7.81 μM, respectively) compared to brasiliencin B (MIC = 1000 nM and 62.5 μM, respectively) that differs at a single stereocenter.

Simon Sieber reposted

Nature Chemical Biology
@natchembio.nature.com

A Review from Sanath Kandy, Michael Pasquale, and Jonathan Chekan highlights newly discovered enzymes responsible for aromatic side-chain crosslinking in ribosomally synthesized and post-translationally modified peptides (RiPPs) www.nature.com/articles/s41...

nature.comAromatic side-chain crosslinking in RiPP biosynthesis - Nature Chemical BiologyAromatic side-chain crosslinking is emerging as a widespread and biosynthetically diverse feature in the RiPP natural products. This Review summarizes and unifies recent advancements, focusing on key ...

Simon Sieber reposted

Stephan Hacker
@stephanhacker2.bsky.social

Interesting paper by the @hoceklab.bsky.social in @commschem.bsky.social. They synthesized NTPs containing a squaric acid monoester monoamide, enzymatically incorporated them into RNA and used the modified RNA for cross-linking to lysines in RNA-binding proteins. www.nature.com/articles/s42...

nature.comEnzymatic synthesis of reactive RNA probes containing squaramate-linked cytidine or adenosine for bioconjugations and cross-linking with lysine-containing peptides and proteins - Communications Chemis...RNA-protein interactions are an essential yet underexplored field of research. Here, the authors design and synthesize squaramate-linked cytidine and adenosine analogues and use them as building block...

Simon Sieber reposted

Dirk Trauner
@dirktrauner.bsky.social

Check out our paper on veratramine and isosteroidal alkaloids, now published in JACS. pubs.acs.org/doi/10.1021/...

pubs.acs.orgConcise Synthesis of (−)-Veratramine and (−)-20-iso-Veratramine via Aromative Diels–Alder ReactionA concise and convergent synthesis of the isosteroidal alkaloids veratramine and 20-iso-veratramine has been accomplished. A Horner–Wadsworth–Emmons olefination joins two chiral building blocks of app...

Simon Sieber reposted

Tom Fiala
@tomfialab.bsky.social

TWeeP (This Week's Paper): In @angewandtechemie.bsky.social Rai et al. disclosed a tripeptide with an N-terminal azide and C-alkyne that can undergo topochemical polymerization in its crystalline form. The material is good at gluing together biological matter. onlinelibrary.wiley.com/doi/epdf/10....

onlinelibrary.wiley.comA Malleable Collagen‐Mimic that Undergoes Moisture‐Induced Hardening for Gluing Hydrophilic SurfacesA collagen-inspired helical protein-mimic has been synthesized via topochemical polymerization of a designed tripeptide monomer. In the monomer crystal, molecules arrange in a head-to-tail manner, fo...
Simon Sieber
@simonsieber.bsky.social

Great opportunity for a PhD student position. I strongly recommend it!

Karl Gademann@karlgademann.bsky.social

We are hiring! Exciting project on the performance enhancement of peptides. Check out and share: jobs.uzh.ch/job-vacancie...

jobs.uzh.chUZH: PhD Student Position in Peptide ChemistryA PhD Student position is available in the group of Prof. Dr. Karl Gademann, located in the Department of Chemistry at the University of Zurich (Switzerland). Our group combines the synthesis of natur...

Simon Sieber reposted

Karl Gademann
@karlgademann.bsky.social

Replying to @karlgademann.bsky.social

Read more in our study published at www.nature.com/articles/s42...

nature.comFunctional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide - Communications ChemistryThe ham gene cluster in Burkholderia cenocepacia H111 produces two compounds: the signalling molecule valdiazen as racemate and the antifungal fragin in enantiopure form. Here, the authors demonstrate...

Simon Sieber reposted

Tom Fiala
@tomfialab.bsky.social

TWeeP (This Week's Paper): Happy new year! I'm back with my weekly highlights after the holiday break. Let's kick off 2025 with some nice bioconjugation work by Esteve, Koniev, Lehn et al. in #JACS. Dynamic imine formation triggers proximity-driven SNAr on proteins. pubs.acs.org/doi/abs/10.1...

pubs.acs.orgSelective Protein (Post-)modifications through Dynamic Covalent Chemistry: Self-activated SNAr ReactionsSNAr reactions were remarkably accelerated using a pretargeting and activating unit based on dynamic covalent chemistry (DCvC). A Cys attack at the C–F bond on the aromatic ring of salicylaldehyde derivatives was only observed upon iminium formation with a neighboring Lys residue of model small peptides. Such self-activation was ascribed to the stronger electron-withdrawing capability of the iminium bond with respect to that of the parent aldehyde that stabilized the transition state of the reaction, together with the higher preorganization of the reactive groups in the cationic aldiminium species. This approach was further applied for the functionalization of two antibodies. In both cases, the presence of the aldehyde group in close proximity to the reactive C–F bond resulted in a noteworthy increase in bioconjugation yields, with excellent chemo-selectivity. Whereas the modification of an IgG1 antibody led to stochastic product distributions, microenvironment selectivity was noted when employing IgG4, in line with the lower number of Lys residues in the hinge region of the latter. Additionally, the postfunctionalization of the modified antibodies was attained through the dynamic covalent exchange of the tethered iminium derivative with hydrazides, representing an unprecedented “tag and modify” selective bioconjugation strategy based on DCvC.

Simon Sieber reposted

Mathias Christmann
@christmann.bsky.social

📊 What I learned from analyzing 3000+ SI PDFs: Only 40% of papers w/ #MassSpectrometry data compliant w/ journal guidelines! From zero #Python experience to an automated checker Read the paper: pubs.acs.org/doi/10.1021/... Try the tool: github.com/match22lab/H... #DataScience #ChemPython #ChemSky

pubs.acs.orgWhat I Learned from Analyzing Accurate Mass Data of 3000 Supporting Information FilesA Python script for the systematic, high-throughput analysis of accurate mass data was developed and tested on more than 3000 Supporting Information (SI) PDFs from Organic Letters. For each SI file, q...

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Thomas Tørring
@thomastorring.bsky.social

A Christmas present to all of the lasso peptide connoisseurs out there. The next chapter in our work is on triculamin is ready on bioRxiv. Great work by two incredibly talented graduate students @amerrild.bsky.social and @tizianasvenningsen.bsky.social. www.biorxiv.org/content/10.1...

biorxiv.orgConvergent Evolution of the Antimycobacterial Lasso Peptide TriculaminTriculamin is a ribosomally synthesized and post-translationally modified peptide (RiPP) lasso peptide with potent antimycobacterial activity, produced by an unusual, non-canonical biosynthetic gene c...

Simon Sieber reposted

Mitja M. Zdouc
@mmzdouc.bsky.social

Are you working on natural products? We’ve just released version 4.0 of the MIBiG data standard and repository! It now includes 3059 biosynthetic gene clusters, thanks to the combined efforts of 288 expert contributors. A thread: (1/8) academic.oup.com/nar/advance-...

academic.oup.comMIBiG 4.0: advancing biosynthetic gene cluster curation through global collaborationAbstract. Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in ag

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ICTC13
@ictc13.bsky.social

Real-Time Observation of Clickable #Cyanotoxin Synthesis in Bloom-Forming #Cyanobacteria Microcystis aeruginosa and Planktothrix agardhii. By Rainer Kurmayer and Rubén Morón Asensio doi.org/10.3390/toxi... #ICTC13

doi.orgReal-Time Observation of Clickable Cyanotoxin Synthesis in Bloom-Forming Cyanobacteria Microcystis aeruginosa and Planktothrix agardhiiRecently, the use of click chemistry for localization of chemically modified cyanopeptides has been introduced, i.e., taking advantage of promiscuous adenylation (A) domains in non-ribosomal peptide s...