Precursor-directed biosynthesis was used to produce analogues of the cyclic depsipeptide mycotoxin beauvericin (1) using the filamentous fungus Beauveria bassiana ATCC 7159. Feeding 30 analogues of D-2-hydroxyisovalerate and L-phenylalanine, the natural 2-hydroxycarboxylic acid and amino acid precursors of beauvericin, led to the biosynthesis of novel beauvericins. Six of these were isolated and characterized, and their cytotoxicity and directional cell migration (haptotaxis) inhibitory activity against the metastatic prostate cancer cell line PC-3M were evaluated. Replacement of one, two, or all three of the D-2-hydroxyisovalerate constituents in beauvericin (1) with 2-hydroxybutyrate moieties (beauvericins G(1-3), compounds 2-4) caused a parallel decline of cell migration inhibitory activity and cytotoxicity, suggesting a requirement for a branched side chain for both of these biological activities at the corresponding positions of beauvericins. Replacement of one, two, or all three N-methyl-L-phenylalanine residues of beauvericin with N-methyl-L-3-fluorophenylalanine moieties (beauvericins H(1-3), compounds 5-7) increased cytotoxicity without affecting antihaptotactic activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/np070262f | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficient and Selective Biosynthesis of a Precursor-Directed FK506 Analogue: Paving the Way for Click Chemistry.
J Nat Prod
March 2025
University of Ljubljana, Biotechnical Faculty, Department of Food Science and Technology, 1000 Ljubljana, Slovenia.
The medically important immunosuppressant FK506 is a structurally complex macrolactone biosynthesized by a combined polyketide synthase and a nonribosomal peptide synthetase enzyme complex. Its acyltransferase domain 4 (AT4) selects an unusual extender unit, resulting in an allyl moiety on carbon 21 of the macrolactone backbone. Based on the AT4 domain, chemobiosynthetic processes have been developed that enable the introduction of diverse moieties at the carbon 21 position.
View Article and Find Full Text PDFBeneficial Soil Fungus Kills Predatory Nematodes with Dehydropeptides Translocating into the Animal Gut.
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 PDFPrecursor-Directed Biosynthesis of Panepoxydone Derivatives with Nitric Oxide Production Inhibitory Activity.
Chembiochem
January 2025
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 PDFExploring the Biosynthetic Potential of Species for Producing Didemnin Antitumor Agents.
ACS 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 PDFDynemicin A Derivatives as Potential Cancer Chemotherapeutics by Mutasynthesis.
Helv 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 PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!