Abstract
Ethyl carbamate (EC) is a potential carcinogen that forms spontaneously during Chinese rice wine fermentation. The primary precursor for EC formation is urea, which originates from both external sources and arginine degradation. Urea degradation is suppressed by nitrogen catabolite repression (NCR) in Saccharomyces cerevisiae. The regulation of NCR is mediated by two positive regulators (Gln3p, Gat1p/Nil1p) and two negative regulators (Dal80p/Uga43p, Deh1p/Nil2p/GZF3p). DAL80 revealed higher transcriptional level when yeast cells were cultivated under nitrogen-limited conditions. In this study, when DAL80-deleted yeast cells were compared to wild-type BY4741 cells, less urea was accumulated, and genes involved in urea utilization were up-regulated. Furthermore, Chinese rice wine fermentation was conducted using dal80Δ cells; the concentrations of urea and EC were both reduced when compared to the BY4741 and traditional fermentation starter. The findings of this work indicated Dal80p is involved in EC formation possibly through regulating urea metabolism and may be used as the potential target for EC reduction.
Highlights
Ethyl carbamate (EC) is a multisite carcinogen described with effects in experimental animals.It was upgraded to Group 2A by the International Agency for Research on Cancer (IARC) in 2007, indicating that it is a probable carcinogen to human health [1]
Comparative transcriptome strategy was conducted to identify the major factor affecting EC metabolism by S. cerevisiae under high nitrogen and low nitrogen conditions; data show that transcriptional factor DAL80p is the most important under two kinds of nitrogen conditions [15])
The different regulatory effect on DUR1,2 and CAR1 by Dal80p reported previously prompted us to ask whether the deletion of DAL80 would remove its regulation of urea degradation
Summary
It was upgraded to Group 2A by the International Agency for Research on Cancer (IARC) in 2007, indicating that it is a probable carcinogen to human health [1]. Several studies have shown that brandy, sake, and sugar cane spirit contained high levels of EC [2,3,4]. An investigation revealed that Chinese rice wine contains higher levels of EC than other alcoholic beverages [5]. Several metabolic pathways have been identified for EC formation. The major precursors participating in the formation of EC include carbamyl groups, such as urea, citrulline, and carbamoyl phosphate [6]. The reaction between urea and ethanol is the most common pathway of EC formation
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