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-α (TNF-α; 72.2%, low-dose MG vs.
model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1β (IL-1β; 76.4%, low-dose MG vs. model),
and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through
the NF-κB 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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