Max Crüsemann

Phylogeny‐Aware Metabologenomics Accurately Assigns Natural Products to Biosynthetic Gene Clusters We report a statistical approach for associating biosynthetic gene clusters with their cognate metabolites and demonstrate its unprecedented power for scalable natural product discovery. Notably, it ...

Phylogeny-­ Aware Metabologenomics Accurately Assigns
Natural Products to Biosynthetic Gene Clusters

@microbiotech.bsky.social by Judith Boldt et al from Ulrich Nübel and @drrolfmueller.bsky.social

enviromicro-journals.onlinelibrary.wiley.com/doi/pdf/10.1...

Discovery, biosynthesis, and bioactivities of peptidic natural products from marine sponges and sponge-associated bacteria Covering 2010 to 2025 Sponges are benthic, sessile invertebrate metazoans that are some of the most prolific sources of natural products in the marine environment. Sponge-derived natural products are…

🔓Don't miss this #OpenAccess review by Eric W. Schmidt, Vinayak Agarwal & co. at @utah.edu & @gtsciences.bsky.social looking at peptidic natural products isolated from the sponge hosts and the associated microbiome #natprod #secmet

Check it out in full on our website🔽

Chemical richness and diversity of uncultivated ‘Entotheonella’ symbionts in marine sponges - Nature Chemical Biology Marine sponges host bacteria that produce diverse bioactive compounds. Here, the authors conduct a large-scale metagenomic, single-bacterial and biochemical study to reveal the untapped biosynthetic p...

Happy to share work by Maria and awesome collaborators published in Nature Chem Bio!
Using metagenomic, single-bacterial, and biochemical methods we provide insights into uncultivated bacterial symbionts as rich sources of bioactive natural products in marine sponges.
#DrugDiscovery #NaturalProducts

Molecules to medicine: advances in metabolomics for natural product drug discovery Recent advances in metabolomics are accelerating natural product (NP) drug discovery. NPs possess diverse biological relevance and comprise a signific…

Molecules to medicine: advances in metabolomics for natural product drug discovery by Victoria Deleray,
Pieter C Dorrestein & Nicole E Avalon
#naturalproducts #secmet #metabolomics
www.sciencedirect.com/science/arti...

Discovery of Late Intermediates in Methylenomycin Biosynthesis Active against Drug-Resistant Gram-Positive Bacterial Pathogens The methylenomycins are highly functionalized cyclopentanone antibiotics produced by Streptomyces coelicolor A3(2). A biosynthetic pathway to the methylenomycins has been proposed based on sequence analysis of the proteins encoded by the methylenomycin biosynthetic gene cluster and the incorporation of labeled precursors. However, the roles played by putative biosynthetic enzymes remain experimentally uninvestigated. Here, the biosynthetic functions of enzymes encoded by mmyD, mmyO, mmyF, and mmyE were investigated by creating in-frame deletions in each gene and investigating the effect on methylenomycin production. No methylenomycin-related metabolites were produced by the mmyD mutant, consistent with the proposed role of MmyD in an early biosynthetic step. The production of methylenomycin A, but not methylenomycin C, was abolished in the mmyF and mmyO mutants, consistent with the corresponding enzymes catalyzing the epoxidation of methylenomycin C, as previously proposed. Expression of mmyF and mmyO in a S. coelicolor M145 derivative engineered to express mmr, which confers methylenomycin resistance, enabled the resulting strain to convert methylenomycin C to methylenomycin A, confirming this hypothesis. A novel metabolite (premethylenomycin C), which readily cyclizes to form the corresponding butanolide (premethylenomycin C lactone), accumulated in the mmyE mutant, indicating the corresponding enzyme is involved in introducing the exomethylene group into methylenomycin C. Remarkably, both premethylenomycin C and its lactone precursor were one to two orders of magnitude more active against various Gram-positive bacteria, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium isolates, than methylenomycins A and C, providing a promising starting point for the development of novel antibiotics to combat antimicrobial resistance.

So cool. Greg Challis shows that a methylenomycin precursor is a better antibiotic than methylenomycin itself. This is in S.coelicolor A3(2)! Probably many similar examples yet to be discovered of pathways intermediates being useful, but consistently overlooked. #secmet

pubs.acs.org/doi/10.1021/...

Growth-coupled microbial biosynthesis of the animal pigment xanthommatin — Led by Leah Bushin, featuring M. Gracia Alvan, @danielvolke.bsky.social @oscarpuiggene.bsky.social in a fantastic collaboration w/Brad Moore @labnikel.bsky.social @natbiotech.nature.com 🦑
www.nature.com/articles/s41...

Discovery and Heterologous Expression of the Soil Metagenome-Derived Lasso Peptide Metanodin with an Unprecedented Ring Structure Culture-independent metagenomic approaches have proven to be effective tools for identifying previously hidden biosynthetic gene clusters (BGCs) encoding novel natural products with potential medical relevance. However, producing these compounds remains challenging as metagenomic BGCs often originate from organisms phylogenetically distant from available heterologous hosts. Lasso peptides, a subclass of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products, exhibit diverse bioactivities, yet no lasso peptide has previously been discovered directly from a metagenome. Here, we report the discovery and heterologous expression of the first soil metagenome-derived lasso peptide. Expression of its biosynthetic gene cluster in Escherichia coli, followed by mass spectrometry analysis, strongly supported the predicted amino acid sequence and lasso structure of the peptide. Notably, this lasso peptide is the first to feature asparagine as the ring-forming residue at position one. Taxonomic analysis of the corresponding BGC identified an uncultivated member of the Steroidobacterales family (Gammaproteobacteria) as the closest known relative of the potential native host. These findings underscore the potential of metagenomic genome mining to reveal structurally novel RiPPs and to expand our understanding of the natural diversity of lasso peptides.

Happy to share our newest manuscript about the discovery and hererologous expression of metanodin, a new lassopeptide with unprecedented structural features directly from soil metagenomes. pubs.acs.org/doi/full/10....
#secmet #lassopeptides #syntheticbiology

Marine Biosciences Assistant/Associate Prof job at University of Florida explore.jobs.ufl.edu/en-us/job/53... [for MNP folks, this is where Sansa Loesgen @loesgenlab.bsky.social is based]

Computational Mass Spectrometry-Based Reassessment of European Amanita sect. Phalloideae Cyclopeptidome An advanced metabolomic workflow featuring expert knowledge-tailored mass spectral queries and multi-informative molecular networking was applied to French DNA-barcoded collections of Amanita species ...

Thrilled to share with you a recent work from our group: Computational Mass Spectrometry-Based Reassessment of European Amanita sect. Phalloideae Cyclopeptidome | Journal of Natural Products pubs.acs.org/doi/10.1021/... Please have a look to the associated MassQL compendium.

IDBac: an open-access web platform and compendium for the identification of bacteria by MALDI-TOF mass spectrometry. https://www.biorxiv.org/content/10.1101/2025.10.15.682631v1

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…

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👇

Awesome work, @mmzdouc.bsky.social !

PhyloNaP: a user-friendly database of Phylogeny for Natural Product-producing enzymes Phylogenetic analysis is widely used to predict enzyme function, yet building annotated and reusable trees is labor-intensive and requires extensive knowledge about the specific enzymes. Existing reso...

Happy to share our newest preprint. PhyloNaP as a user friendly database of phylogeny for enzymes involved in natural product production and as public repository for well curated phylogenetic trees. Happy Tree Building!!!
#phylogeny #secmet #bioinformatics

www.biorxiv.org/content/10.1...

(I have one too! Probably lots of overlap...)

And check out the Secondary Metabolism feed. Lots of awesome science here on Bluesky!
bsky.app/profile/did:...

@mitjare.bsky.social kicking off the second day of the VAAM Workshop at @freieuniversitaet.bsky.social talking about the phyllosphere, its bacterial inhabitants and the natural products they produce - including surfactants!

PhyloNaP: a user-friendly database of Phylogeny for Natural Product-producing enzymes Phylogenetic analysis is widely used to predict enzyme function, yet building annotated and reusable trees is labor-intensive and requires extensive knowledge about the specific enzymes. Existing reso...

PhyloNaP: a user-friendly database of Phylogeny for Natural Product-producing enzymes
doi.org/10.1101/2025...

Congrats to the poster prize!🥳

Just wrapped up inspiring days of science and networking at the VAAM Workshop “Biology of Bacteria Producing Natural Products” in Berlin!
Our team’s first conference ended on a high note — 2nd prize for best poster! 🥈🥳
Thanks to the organizers @niedermeyer-lab.bsky.social for a fantastic meeting. 🙏

Biosynthesis of biologically active terpenoids in the mint family (Lamiaceae) Covering: 2000 to 2025The Lamiaceae family, the sixth largest among angiosperms, is renowned for its rich diversity of terpenoids, many of which exhibit remarkable bioactivities, including anti-inflam...

pubs.rsc.org/en/content/a...

We just published the paper Biosynthesis of biologically active terpenoids in the mint family (Lamiaceae) in Natural Products Reports.

Thanks to everyone involved! :)

Metagenomic Identification of Brominated Indole Biosynthetic Machinery from Cyanobacteria Halogenated indole natural products have been isolated from a variety of organisms, including plants, marine algae, marine invertebrates, and bacteria. Aquatic cyanobacteria, in particular, are rich producers of brominated indoles, but their cognate biosynthetic enzymes have only been successfully linked in a limited number of natural products, such as the eagle-killing toxin aetokthonotoxin (AETX). The biosynthetic pathway for AETX involves five enzymes, two of which were previously undescribed due to incomplete annotations as hypothetical proteins. Our recent elucidation of AETX biosynthesis established functions of the two previously unknown proteins as enzymes responsible for tryptophan halogenation (AetF) and nitrile synthesis (AetD). Given their sequence novelty, we queried metagenomic data sets for these two enzymes and identified two new cyanobacterial haloindole biosynthetic gene clusters (BGCs) from marine sediment in Moorea, French Polynesia, and soil-derived samples in Maunawili Falls, Hawaii. We characterized the recovered BGCs by biochemically validating a new AetF homologue that exclusively halogenates free indole, rather than tryptophan as observed in AETX biosynthesis, and a new AetD homologue that harbors distinct substrate preferences, expanding the scope of nitrile biosynthesis. Additional characterization of core and accessory enzymes within these AETX-like BGCs highlights the breadth and diversity of haloindole biosynthetic machinery in cyanobacteria.

New work led by the amazing @aprillukowski.bsky.social lab. Love working on these interdisciplinary projects discovering new chemical diversity in nature. Microbes are the best chemists!

pubs.acs.org/doi/10.1021/...

Phylogenomics and metabolic engineering reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis Nature Communications - Withanolides are plant steroids with potent bioactivities found in many medicinal plants including Withania somnifera, but their biosynthetic pathway is largely unknown....

Extremely happy to see our withanolide biosynthesis paper out in @natcomms.nature.com‬ rdcu.be/evHOF
Fantastic team effort with the Pucker group @bpucker.bsky.social‬ @puckerlab.bsky.social‬ at @unibonn.bsky.social and Heretsch, Herde and Witte groups at @unihannover.bsky.social. Funded by @dfg.de

A widespread metabolic gene cluster family in metazoans - Nature Chemical Biology Grayson et al. report the genomic discovery and biochemical characterization of a widely distributed gene cluster family for briarane diterpenoid biosynthesis in metazoans. This study expands our unde...

A new paper reports the genomic discovery and biochemical characterization of a widely distributed gene cluster family for briarane diterpenoid biosynthesis in metazoans

www.nature.com/articles/s41...

On the left, a picture of a Petri dish showing an amycalotopsis from which comes in the center, a cartoon dragon and under the dragon the molecules called Dracomycins, which are drawn in the shape of the dragon. On the right a petri dish showing a cartoon of zones of inhibition.

Dracomicins, Hybrid Oligosaccharide–Nonribosomal Peptide Antibiotics from Amycolatopsis Species

pubs.acs.org/doi/10.1021/...

Save the date!

Ultra-deep long-read metagenomics captures diverse taxonomic and biosynthetic potential of soil microbes Background Soil ecosystems have long been recognized as hotspots of microbial diversity, but most estimates of their complexity remain speculative, relying on limited data and extrapolation from shall...

New preprint: we sequenced one soil sample with ultra-deep hybrid metagenomics and found…
→ 800+ MAGs
→ 11,000+ BGCs
→ and still nowhere near saturation.
Soil is wild.
Preprint here: www.biorxiv.org/content/10.1...
#microbiome #metagenomics #BGCs #naturalproducts #secmet

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.

Professor (W3) in Organic Synthesis - Frankfurt am Main, Hessen (DE) job with Johann Wolfgang Goethe-Universität Frankfurt | 12838450 Goethe University Frankfurt am Main invites applications for the position of Professor (W3) in Organic Synthesis at the Faculty of Biochemistry, Ch...

📢 The University of Frankfurt (Germany) is hiring a Full Professor in Organic Synthesis

-->Cutting-edge research in an open, collaborative environment? Check out the call and join one of Germany’s leading research universities.

#AcademicJobs #FacultyPosition

www.nature.com/naturecareer...

A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome Nature - 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...

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

Ribosomal pentapeptide nitration for non-ribosomal peptide antibiotic precursor biosynthesis We discovered and characterized the biosynthesis of the noncanonical 3-nitrotyrosine building block found in the potent non-ribosomal antituberculosis peptide antibiotic rufomycin. In this pathway, a ...

Hybrid does the trick-Happy to share our latest paper on the biosynthesis of the nitro-Tyr residue in the nonribosomal anti-TB antibiotic rufomycin that involved unexpected RiPP precursor nitration. Congrats to all authors and great collaboration with Max Cryle!
www.cell.com/chem/fulltex...

It’s not every day one gets to publish an article with NASA astronauts. This journey started in 2019 and withe the goal to understand the microbial and chemical make-up of the space station. We had lots of experience with analysis from swabs on earth.