A combination of NMR spectroscopy and molecular modeling has been employed to characterize the conformation and dynamics of the macrolide ring in verrucarin A and roridin A, two closely related toxins in the trichothecene mycotoxin family. Longitudinal carbon-13 relaxation times demonstrate the relative flexibility of the macrolide ring. The calculations, NOEs, and scalar vicinal coupling constants show that verrucarin A in CDCl 3 and CD 2Cl 2 predominantly adopts a single, well-defined conformation that matches the crystal structure. In contrast, roridin A is present as a mixture of two conformers.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/np070562x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enzymatic ester bond formation strategies in fungal macrolide skeletons.
Nat Prod Rep
January 2025
College of Pharmaceutical Sciences, Southwest University, 400715 Chongqing, China.
Covering: up to August 2024Macrolides, the core skeletons of numerous marketed drugs and bioactive natural products, have garnered considerable scientific interest owing to their structural diversity and broad spectrum of pharmaceutical activities. The formation of intramolecular ester bonds is a critical biocatalytic step in constructing macrolide skeletons. Here, we summarised enzymatic ester bond formation strategies in fungal polyketide (PK)-type, nonribosomal peptide (NRP)-type, and PK-NRP hybrid-type macrolides.
View Article and Find Full Text PDFCrystal structure of cytochrome P450 NysL and the structural basis for stereo- and regio- selective oxidation of antifungal macrolides.
J Biol Chem
January 2025
Department of Chemistry, University of California, Davis, California 95616, United States.
NysL, a cytochrome P450 monooxygenase from the Gram-positive bacterium Streptomyces noursei, catalyzes the C10 hydroxylation of 10-deoxynystain to nystatin A, a clinically important antifungal. In this study, we present the 2.0 Å resolution crystal structure of NysL bound to nystatin A.
View Article and Find Full Text PDFMolecular Decoration and Unconventional Double Bond Migration in Irumamycin Biosynthesis.
Antibiotics (Basel)
December 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, Moscow 117997, Russia.
Irumamycin (Iru) is a complex polyketide with pronounced antifungal activity produced by a type I polyketide (PKS) synthase. Iru features a unique hemiketal ring and an epoxide group, making its biosynthesis and the structural diversity of related compounds particularly intriguing. In this study, we performed a detailed analysis of the biosynthetic gene cluster (BGC) to uncover the mechanisms underlying Iru formation.
View Article and Find Full Text PDFTotal Synthesis of Exiguolide Stereoisomers: Impact of Stereochemical Permutation on Reactivity, Conformation, and Biological Activity.
J Org Chem
January 2025
Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
(-)-Exiguolide is a marine macrolide natural product with potent anticancer activity. In this study, the total synthesis of exiguolide stereoisomers, (9)-exiguolide, (9,13)-exiguolide, and (9,13,19)-exiguolide, was achieved by capitalizing on our macrocyclization/transannular pyran cyclization strategy. The impact of the stereochemical permutation on the reactivity of advanced intermediates, the conformation of the macrocyclic skeleton, and the antiproliferative activity against human cancer cells were investigated in detail.
View Article and Find Full Text PDFGoniodomic Acid, a Transient Oxirane Intermediate in the Conversion of the Macrolide Algal Toxin Goniodomin A to Seco Acids.
Chem Res Toxicol
January 2025
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
The algal macrolide goniodomin A (GDA) undergoes ring-cleavage under unusually mild, alkaline conditions to form mixtures of stereoisomers of seco acids GDA-sa and iso-GDA-sa. In the primary fragmentation pathway, opening of the macrolide ring occurs by displacement of the carboxyl group by a base-catalyzed attack of the C32 hemiketal hydroxy group on C31, yielding an oxirane-carboxylic acid, named goniodomic acid. The oxirane ring is unstable, undergoing solvolytic opening to form mainly GDA-sa.
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!