Biology subjects

Surup, F.

Publications and source records attributed to Surup, F..

4 recordsLinked to original sources

bioRxiv2026

Natural product-derived azaphilones are selective scaffolds for covalent lysine liganding in live cells

Lysine-directed covalent liganding offers a promising strategy to expand the covalently ligandable proteome beyond cysteine. However, broadly applicable and selective lysine-reactive scaffolds remain limited. Here, we designed SCL-alkyne, a simplified azaphilone probe derived from the natural product sclerotiorin (SCL), for the global profiling of lysine reactivity in bacteria. SCL-alkyne displayed high intrinsic selectivity for lysine in vitro and in live Escherichia coli cells. In situ proteome profiling revealed that 84% of engaged sites belong to lysine residues and the protein N-terminus. Reactivity mapping provided an inventory of highly reactive sites showing that only a limited subset of reactive lysines is located in functional regions of proteins. Analysis of proteins enriched via the SCL-alkyne probe unraveled bacterial chemotaxis as a major target pathway which was confirmed by an impaired chemotactic response upon treatment of bacteria with SCL-alkyne. Competitive profiling of three structurally related azaphilone natural products identified 60 protein targets belonging to pathways related to iron-sulfur cluster assembly and antioxidant function. This study not only highlights the diverse modes-of-action of natural product azaphilones, but also establishes its core scaffold as effective lysine-reactive chemotype for identifying ligandable lysines.

biochemistry↗

bioRxiv2026

Bootstrap resampling of mass spectral pairs with SpecReBoot reveals hidden molecular relationships

Mass spectral molecular networking organizes tandem mass spectrometry (MS/MS) data by connecting spectra based on similarity scores. However, these deterministic metrics provide no measure of uncertainty, so molecular networks often retain edges arising from noise or missing fragments, while authentic chemical relationships may remain obscured. To address this gap, we present SpecReBoot, a statistical framework that adapts Felsensteins bootstrap principle to MS/MS similarity scoring. By resampling fragment-level features and recomputing similarity across replicates, SpecReBoot transforms a single score into a confidence distribution and assigns bootstrap support to network edges. Using large, curated MS/MS spectral datasets, we demonstrate that SpecReBoot systematically removes unreliable connections and recovers robust low-similarity links, refining networks and revealing hidden relationships. We highlight how this confidence-aware "rebooting" guided the discovery of an unprecedented macrolactone scaffold from the endophytic fungus Diaporthe caliensis. Altogether, SpecReBoot provides the first general framework for quantifying confidence in MS/MS similarity and molecular network analysis.

biochemistry↗

bioRxiv2024

Elucidation of the life cycle of a saprotrophic inoperculate discomycete that is associated with pinesap, using a polyphasic taxonomic approach

This study deals with the elucidation of the life cycle of an inoperculate discomycete that was eventually collected from conifer wood in South Germany and has become famous for the extraordinary diversity of its secondary metabolites when it was studied extensively during the 1990s. It had then been identified as Lachnum papyraceum (Lachnaceae, Helotiales) based on morphological traits, and extracts from its mycelial cultures were found to possess extraordinary nematicidal and antibiotic activities. Over 60 different secondary metabolites were finally identified from this fungus after extensive variation of culture media and scale up of production up to 100 litre scale. Among the main active principles were mycorrhizin A and chloromycorrhizin A, which had first been reported in 1987 from an unnamed "mycorrhizal" fungus of the hemiparasitic plant, Monotropa hypopitys (pinesap) that was isolated in Sweden. We noted that both the Lachnum strain and the original mycorrhizin producer were still available in the public domain, and decided to study them for comparison, using a multilocus phylogeny and also generated secondary metabolite profiles of both strains using analytical high performance liquid chromatography coupled to diode array and mass spectrometric detection (HPLC-DAD/MS). Surprisingly, the sequence data as well as the secondary metabolite profiles of both strains were highly similar, and it was also confirmed by phylogenetic methods that the strains are indeed nested within the genus Lachnum by comparison of their ITS, LSU and RBP2 sequences. The specimen called L. papyraceum in the old publications was tentatively re-identified by Hans-Otto Baral as L. cf. subvirgineum, but substantial further work on the taxonomy of the genus remains to be done, anyway. We conclude that some Lachnum species have a highly complex but all the more interesting life cycle, and the mycorrhizal symbiont partner may invade the host plant, where it may persist as an endophyte and finally turn saprotrophic on the wood of the senescent pine tree. The taxonomy of these fungi should also be further resolved in the future, using a polythetic concept that includes chemotaxonomic data and a multi-locus genealogy.

ecology↗

bioRxiv2019

Cycloheximide-Producing Streptomyces Associated with Xyleborinus saxesenii and Xyleborus affinis Fungus-Farming Ambrosia Beetles

Symbiotic microbes help a myriad of insects acquire nutrients. Recent work suggests that insects also frequently associate with actinobacterial symbionts that produce molecules to help defend against parasites and predators. Here we explore a potential association between Actinobacteria and two species of fungus-farming ambrosia beetles, Xyleborinus saxesenii and Xyleborus affinis. We isolated and identified actinobacterial and fungal symbionts from laboratory reared nests, and characterized small molecules produced by the putative actinobacterial symbionts. One 16S rRNA phylotype of Streptomyces (XylebKG-1) was abundantly and consistently isolated from the nests and adults of X. saxesenii and X. affinis nests. In addition to Raffaelea sulphurea, the symbiont that X. saxesenii cultivates, we also repeatedly isolated a strain of Nectria sp. that is an antagonist of this mutualism. Inhibition bioassays between S. griseus XylebKG-1 and the fungal symbionts from X. saxesenii revealed strong inhibitory activity of the actinobacterium towards the fungal antagonist Nectria sp. but not the fungal mutualist R. sulphurea. Bioassay guided HPLC fractionation of S. griseus XylebKG-1 culture extracts, followed by NMR and mass spectrometry identified cycloheximide as the compound responsible for the observed growth inhibition. A biosynthetic gene cluster putatively encoding cycloheximide was also identified in S. griseus XylebKG-1. The consistent isolation of a single 16S phylotype of Streptomyces from two species of ambrosia beetles, and our finding that a representative isolate of this phylotype produces cycloheximide, which inhibits a parasite of the system but not the cultivated fungus, suggests that these actinobacteria may play defensive roles within these systems.

microbiology↗