Tropone is a seven-membered ring nonbenzenoid aromatic compound. It is the core structure of tropolonoids, which have various biological activities. In this study, a hybrid tropone biosynthetic pathway was designed by connecting phenylacetic acid (PAA) degradation with its biosynthesis and reconstituted in Escherichia coli. To simplify pathway construction and optimization, the use of E. coli endogenous genes was maximized and only three exogenous genes were employed. The entire pathway was divided into four modules: the endogenous shikimate pathway module, the hybrid PAA biosynthetic module, the endogenous PAA catabolic module and the heterogeneous tropone biosynthetic module. Efficiency of the PAA catabolic module was enhanced using PAA consumption rate as the indicator. Then, a single point mutation was introduced to inactivate the ALDH domain of PaaZ and the carbon flow was redirected toward tropone synthesis. Assembly of the full pathway led to de novo tropone production with the best titer of 65.2 ± 1.4 mg/L in shake flask experiment. This study provides a potential alternative for sustainable production of tropone and its derivatives.
BackgroundHyperuricemia is generally defined as the high level of serum uric acid and is well known as an important risk factor for the development of various medical disorders. However, the medicinal treatment of hyperuricemia is frequently associated with multiple side-effects.MethodsThe therapeutic effect of noni (Morinda citrifolia L.) fruit juice on hyperuricemia and the underlying molecular mechanisms were investigated in mouse model of hyperuricemia induced by potassium oxonate using biochemical and high-throughput RNA sequencing analyses.ResultsThe levels of serum uric acid (UA) and xanthine oxidase (XOD) in mice treated with noni fruit juice were significantly decreased, suggesting that the noni fruit juice could alleviate hyperuricemia by inhibiting the XOD activity and reducing the level of serum UA. The contents of both serum creatinine and blood urine nitrogen of the noni fruit juice group were significantly lower than those of the model group, suggesting that noni fruit juice promoted the excretion of UA without causing deleterious effect on the renal functions in mice. The differentially expressed microRNAs involved in the pathogenesis of hyperuricemia in mice were identified by RNA sequencing with their target genes further annotated based on both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases to explore the metabolic pathways and molecular mechanisms underlying the therapeutic effect on hyperuricemia by noni fruit juice.ConclusionOur study provided strong experimental evidence to support the further investigations of the potential application of noni fruit juice in the treatment of hyperuricemia.
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