Yin Wan

Hyperuricemia, a diet-related metabolic disorder, is primarily managed by targeting xanthine oxidase (XOD), the central enzyme responsible for uric acid production.

The flavor and scent of Chinese Baijiu are closely linked to the quantity of fatty acid ethyl esters, and their generation is closely associated with Baijiu brewing yeast, most notably ethyl acetate (EA) and ethyl hexanoate (EH). At present, however, the specific mechanism of EA and EH produced by Wickerhamomyces anomalus under ethanol stress during the brewing of Baijiu remains unclear. Our study findings revealed that ethanol stress inhibited the generation of precursor substances (pyruvate and acetyl-CoA) in the fatty acid ethyl ester biosynthesis pathway of W. anomalus NCU003. The high level of EA produced in the fatty acid ethyl ester biosynthesis pathway was associated with the enhanced expressions of ATF1 and EAT1 and the increased activity of C2 esterase under 3% and 6% ethanol stress. The lower EA content was related to the high expression of IAH1 and low activity of C2 esterase under 9% ethanol stress. We also found that the expression of ACC, FAS1, FAS2, EHT1, and EEB1 was up-regulated, which may promote the synthesis of EH under ethanol stress, whereas the activity of C6 esterase may have no effect on the synthesis of EH. Our study results indicated that the above genes and C2 esterase can be modulated in W. anomalus NCU003 under ethanol stress, thus promoting the synthesis of fatty acid ethyl esters during the brewing of Baijiu.

Hyperuricemia (HUA), a metabolic disorder, is clinically defined by sustained elevation of serum uric acid (SUA), arising from either dysregulation of impaired renal excretion or purine metabolism. Over the past few years, nutritional interventions have garnered increasing attention for their potential role in the management of chronic metabolic diseases. In this study, a multi-level research strategy, integrating in silico simulations, in vitro enzymatic inhibition assays, cellular models, and animal experiments, was employed to systematically compare the urate-lowering effects of vitamin B6 (VB6), B9 (VB6), and B12 (VB6). The results demonstrated that all three B vitamins significantly reduced SUA levels in hyperuricemic mice. Among them, VB9 exhibited the most potent urate-lowering effect through its superior inhibitory activity against xanthine oxidase (XOD), with an IC50 value of 3.00 mM (95% CI: 2.61-3.33 mM). Furthermore, VB9 effectively ameliorated systemic inflammation, restored dysregulated energy and lipid metabolism, and re-established hepatic purine metabolic homeostasis in hyperuricemic mice, potentially through a systemic regulatory network mediated by one-carbon metabolism. Therefore, these results demonstrate the distinct urate-lowering potential of VB9 and provides novel insights into nutritional intervention strategies for managing metabolic disorders.

During the solid-state brewing process of traditional Chinese Baijiu, lactic acid is the most abundant organic acid, which inhibits the growth and metabolism of Saccharomyces cerevisiae. To reveal the lactic acid tolerance mechanism of S. cerevisiae, the growth, metabolic performance, and antioxidant enzyme activity of S. cerevisiae NCUF309.5-44 and S. cerevisiae NCUF309.5 were measured under 4% (v/v) lactic acid stress. Additionally, whole-genome re-sequencing and transcriptomic analyses were performed to identify genetic variations and differentially expressed genes between the two strains under lactic acid stress. The results showed that, compared to the original strain, S. cerevisiae NCUF309.5-44 could adapt to the lactic acid stress faster, with a superior utilization rate of reducing sugar and a 6.43-fold higher ethanol production at 16 h. The strain primarily activated the GSH/GPx system, resulting in a 37.29% lower intracellular ROS content. A total of 1087 SNPs and 698 InDels were found between the strains, with 384 genes significantly upregulated and 254 genes downregulated in the S. cerevisiae NCUF309.5-44 under lactic acid stress. S. cerevisiae NCUF309.5-44 responded to lactic acid stress by activating the pheromone response pathway and the cell wall integrity pathway. Meanwhile, the capacity of strains to maintain the cell membrane and proton extrusion was strengthened. Additionally, its glycolysis/gluconeogenesis metabolism was also enhanced. All these mechanisms collectively contributed to improving the lactic acid tolerance of S. cerevisiae NCUF309.5-44. These findings not only enhanced our understanding of lactic acid tolerance mechanisms of S. cerevisiae NCUF309.5-44 but also paved the way for the application of this strain in optimizing Baijiu production.