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

Abstract. Secondary or specialized metabolites show extraordinary structural diversity and potent biological activities relevant for clinical and industria

Toxic benthic cyanobacterial mats have been identified globally as a potential health hazard since they can produce potent cyanotoxins. Such mats have…

Peptides are highly selective organocatalysts, with intrinsic modularity allowing precise control over structure and function. Advances in peptide synthesis, biotechnology, and cheminformatics will en...

Antibiotic resistance presents a growing global health crisis, demanding new therapeutic strategies that target novel bacterial mechanisms. Recent advances in protein structure prediction and machine ...

A 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.

Flow cytometry has great potential for screening in translational research areas due to its deep quantification of cellular features, ability to colle…

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 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...

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

The 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.

Covering: 1994 to 2024Historically, microbial natural product discovery has been predominantly guided by biological activity from crude microbial extracts with metabolite characterization proceeding o...

Strigolactones (SLs) are methylbutenolide molecules derived from β-carotene through an intermediate carlactonoic acid (CLA). Canonical SLs act as signals to microbes and plants, whereas noncanonical S...

Rapid 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.

Aromatic 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 ...

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...

A 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...

The rapid emergence of antimicrobial-resistant pathogenic microbes has accelerated the search for novel therapeutic agents. Here we report the discovery of antarmycin A (1), an antibiotic containing a...

A 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...

A 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...

Duncan lab

The 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...

SNAr 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.

A 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...

Triculamin 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...

Abstract. Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in ag

Recently, 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...