Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

A hybrid -AT PKS/NRPS gene cluster was identified with defined boundaries for hangtaimycin biosynthesis in CPCC200148. Deoxyhangtaimycin, a new derivative of hangtaimycin, was identified from the gene knockout mutant. In vitro biochemical assays demonstrated that the cytochrome P450 monooxygenase Htm11 was responsible for the stereoselective hydroxylation of deoxyhangtaimycin to hangtaimycin. More importantly, deoxyhangtaimycin showed activity against influenza A virus at the micromolar level, highlighting its potential as an antiviral lead compound.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.2c00242DOI Listing

Publication Analysis

Top Keywords

cytochrome p450
8
p450 monooxygenase
8
hangtaimycin biosynthesis
8
monooxygenase catalyzing
4
catalyzing c-42
4
c-42 hydroxylation
4
hydroxylation glycine-derived
4
glycine-derived fragment
4
hangtaimycin
4
fragment hangtaimycin
4

Similar Publications

Sterols are essential isoprenoid derivatives that contribute to membrane structure and function. In plants, they also serve as precursors to phytohormones and specialized metabolites important for development, defense, and health. Although the sterol biosynthetic pathway is considered well-characterized, we report the discovery of a plant-specific cytochrome -like protein, CB5LP, as a critical component of phytosterol biosynthesis.

View Article and Find Full Text PDF

Species-specific gene expression manipulation in humanized livers of chimeric mice via siRNA-encapsulated lipid nanoparticle treatment.

Mol Ther Methods Clin Dev

June 2025

Eisai Co., Ltd., Tsukuba Research Laboratories, 5-1-3, Tokodai, Tsukuba, Ibaraki 300-2635, Japan.

Liver-humanized chimeric mice (PXB-mice) are widely utilized for predicting human pharmacokinetics (PK) and as human disease models. However, residual metabolic activity of mouse hepatocytes in chimeric mice can interfere with accurate human PK estimation. Lipid nanoparticle (LNP)-formulated small interfering RNA (siRNA) treatment makes it possible to eliminate the shortcomings of chimeras and create new models.

View Article and Find Full Text PDF

Introduction: Tenvermectin (TVM) is a novel avermectin-class drug that has attracted attention for its superior antiparasitic potency, low toxicity, and broad-spectrum activity. However, uncertainty about its interaction with cytochrome P450 enzymes (CYPs) has raised concerns about potential therapeutic failure, increased risk of toxicity, dangerous drug combinations, and prolonged discontinuation periods.

Method: To address these critical safety concerns, we conducted a systematic comparative study using a highly selective and quantitatively accurate substrate conversion assay to assess and compare the effects of TVM and ivermectin (IVM) on the activities of key CYPs (CYP1A1/2, 2B1, 2C6, 2D2, and 3A1/2).

View Article and Find Full Text PDF

Genetic variants of various cytochrome P450 (CYP) enzymes significantly impact pharmacokinetics. The highly polymorphic hepatic CYP2C9 metabolizes ~ 15% of clinically used drugs. This study aimed to characterize the ligand-binding properties of the understudied CYP2C9.

View Article and Find Full Text PDF

Ambroxol (AMB), a common expectorant, enters aquatic environments via wastewater, yet its ecological risks remain unclear. Under UV exposure (15 mJ·cm, λ = 185-400 nm), AMB undergoes photolysis, among the photoproducts, 4-((2-amino-3-bromobenzyl)amino) cyclohexanol (P1) and 2-amino-3,5-dibromobenzaldehyde (DBA) are major species, comprising over 50% of the total photoproduct peak area at the photolytic plateau. Acute toxicity tests with AMB, P1, and DBA in four aquatic species at different trophic levels revealed: the highest sensitivity in (LC = 0.

View Article and Find Full Text PDF