Biosynthesis of Chryseno[2,1,c]oxepin-12-Carboxylic Acid from Glycyrrhizic Acid in Aspergillus Terreus TMZ05-2, and Analysis of Its Anti-inflammatory Activity.
Journal of microbiology(2024)
摘要
Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-alpha (TNF-alpha; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1 beta (IL-1 beta; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-alpha, P-IKB-alpha, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-kappa B pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.
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关键词
Glycyrrhizic acid,Glycyrrhizic acid derivatives,Aspergillus terreus,Anti-inflammatory activity,NO release,Lactone biosynthesis
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