A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (-) from RJ2. Structure elucidation was conducted using NMR and HRESIMS analysis, and the absolute configuration was determined by advanced Marfey's method, Mosher's analysis, and ECD analysis. The obtained compounds revealed selective and significant cytotoxicity, specifically against colorectal cancer cells bearing the K-ras mutation, with IC values ranging from 40 nM to 3.5 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.4c00013 | DOI Listing |
J Am Chem Soc
December 2024
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstraße 11a, 07745 Jena, Germany.
is a mold fungus that has gained attention for its positive correlation with soil health, plant growth, and applications as a crop biocontrol agent to suppress the threats of nematode pests. To date, the mechanisms underlying the protective traits of against these plant parasites have remained elusive. Here we report that abundantly produced peptidic biosurfactants, malpinin A-D, exhibit robust inhibitory activity against nematodes.
View Article and Find Full Text PDFChembiochem
October 2024
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou, 730000, P. R. China.
Panepoxydone is a natural NF-κB inhibitor isolated from basidiomycetes belonging to the genus Panus and Lentinus. It is biosynthesized from prenylhydroquinone through successive hydroxylation, epoxidation, and reduction reactions. In this study, we establish an efficient precursor-directed biosynthesis strategy for the structural expansion of panepoxydone based on its biosynthetic pathway.
View Article and Find Full Text PDFACS Chem Biol
October 2024
Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
Didemnins are a class of cyclic depsipeptides derived from sea tunicates that exhibit potent anticancer, antiviral, and immunosuppressive properties. Although certain species can produce didemnins, their complete biosynthetic potential remains largely unexplored. In this study, we utilize feature-based molecular networking to analyze the metabolomics of and , focusing on the production of didemnin natural products.
View Article and Find Full Text PDFHelv Chim Acta
December 2023
Department of Chemistry, Remsen Hall, The Johns Hopkins University, 3400 North Charles St., Baltimore, MD 21218, USA.
The enediyne antitumor antibiotics have remarkable structures and exhibit potent DNA cleavage properties that have inspired continued interest as cancer therapeutics. Their complex structures and high reactivity, however, pose formidable challenges to their production and development in the clinic. We report here proof-of-concept studies using a mutasynthesis strategy to combine chemical synthesis of select modifications to a key iodoanthracene-γ-thiolactone intermediate in the biosynthesis of dynemicin A and all other known anthraquinone-fused enediynes (AFEs).
View Article and Find Full Text PDFMethods Enzymol
August 2024
School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia. Electronic address:
Siderophores are low-molecular-weight organic bacterial and fungal secondary metabolites that form high affinity complexes with Fe(III). These Fe(III)-siderophore complexes are part of the siderophore-mediated Fe(III) uptake mechanism, which is the most widespread strategy used by microbes to access sufficient iron for growth. Microbial competition for limited iron is met by biosynthetic gene clusters that encode for the biosynthesis of siderophores with variable molecular scaffolds and iron binding motifs.
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