Abstract. This study investigates the impact of incorporating stereochemical information, a crucial aspect of computational drug discovery and materials de

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.

Abstract. This study investigates the impact of incorporating stereochemical information, a crucial aspect of computational drug discovery and materials de

Terrestrial analog environments and their microbial communities are key elements to prepare for the exploration of extraterrestrial planetary environments that potentially sustained, or even may still...

Bacteria of the phylum Actinomycetota are extremely diverse: They inhabit niches ranging from soils and ocean sediments to the normal human microbiota, and they cause tuberculosis, one of the most pre...

The structural complexity of natural products arises from the complexity of their biosynthetic pathways and directly contributes to their biological activities. Guided by this principle, we screened 5...

Nuclear magnetic resonance (NMR) data provides rich quantum information on molecular structure, which is closely related to chemical structure and widely used for structural characterization in chemic...

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 ...

Streptoclipamide A, a potent ClpP inhibitor (IC50 = 480 nM), was discovered by self-resistance-guided genome mining coupled with dual functional screening. It uniquely suppresses MRSA virulence toxin...

Covering: up to 2025This review explores the potential of bioinformatics and chemoinformatics tools to advance the exploration of natural extracts libraries (NELs). Although metabolomics has become a ...

Tandem mass spectrum to decision (MS2DECIDE) leverages decision theory and expert knowledge to aggregate the outputs of three widely used annotation tools (GNPS, Sirius, and ISDB-LOTUS) and compute a...

A significant bottleneck in metabolomics data interpretation is the effective use of domain knowledge to assign structural information based on fragmentation patterns. The mass spectrometry query lang...

Haouamines are highly constrained marine alkaloids possessing a unique in nature skeleton. The high degree of complexity of such alkaloids raises questions about their chemical assembly. This is addre...

New observations fail to confirm signs of life in the atmosphere of the distant planet K2-18b. They also raise questions about what it will take to detect biology light-years away.

Annotation is the process of assigning features in mass spectrometry metabolomics data sets to putative chemical structures or “analytes.” The purpose of this study was to identify challenges in the a...

Covering: 1982 up to the end of 2024 Marine exometabolites (EMs) are small molecules released by marine (micro)organisms into the seawater. Collectively, all of the released EMs contribute to the…

Nature remains a vast repository of complex and functional metabolites whose structural characterization continues to drive innovations in pharmaceuticals, agrochemicals, and materials science. The cr...

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, constitutes an effective and widely used treatment for type 2 diabetes and obesity. However, challenges such as insufficient oral bioav...