Deciphering the Crucial Roles of the Quorum-Sensing Transcription Factor SdiA in NADPH Metabolism and (S)-Equol Production in Escherichia coli Nissle 1917
文献类型: 外文期刊
作者: Wang, Zhe 1 ; Dai, Yiqiang 1 ; Azi, Fidelis 3 ; Dong, Mingsheng 1 ; Xia, Xiudong 1 ;
作者机构: 1.Nanjing Agr Univ, Coll Food Sci & Technol, Nanjing 210095, Peoples R China
2.Jiangsu Acad Agr Sci, Inst Agroprod Proc, Nanjing 210014, Peoples R China
3.Guangdong Technion Israel Inst Technol, Dept Chem Engn, Shantou 515063, Peoples R China
4.Minist Sci & Technol, Jiangsu Key Lab Food Qual & Safety, State Key Lab Cultivat Base, Nanjing 210014, Peoples R China
5.Jiangsu Univ, Sch Food & Biol Engn, Zhenjiang 212013, Peoples R China
关键词: isoflavone; (S)-equol; quorum sensing; E. coli Nissle 1917; NADPH; biosynthesis
期刊名称:ANTIOXIDANTS ( 影响因子:7.0; 五年影响因子:7.3 )
ISSN:
年卷期: 2024 年 13 卷 3 期
页码:
收录情况: SCI
摘要: The active metabolite (S)-equol, derived from daidzein by gut microbiota, exhibits superior antioxidative activity compared with its precursor and plays a vital role in human health. As only 25% to 50% of individuals can naturally produce equol when supplied with isoflavone, we engineered probiotic E. coli Nissle 1917 (EcN) to convert dietary isoflavones into (S)-equol, thus offering a strategy to mimic the gut phenotype of natural (S)-equol producers. However, co-fermentation of EcN-eq with fecal bacteria revealed that gut microbial metabolites decreased NADPH levels, hindering (S)-equol production. Transcriptome analysis showed that the quorum-sensing (QS) transcription factor SdiA negatively regulates NADPH levels and (S)-equol biosynthesis in EcN-eq. Screening AHLs showed that SdiA binding to C10-HSL negatively regulates the pentose phosphate pathway, reducing intracellular NADPH levels in EcN-eq. Molecular docking and dynamics simulations investigated the structural disparities in complexes formed by C10-HSL with SdiA from EcN or E. coli K12. Substituting sdiA_EcN in EcN-eq with sdiA_K12 increased the intracellular NADPH/NADP+ ratio, enhancing (S)-equol production by 47%. These findings elucidate the impact of AHL-QS in the gut microbiota on EcN NADPH metabolism, offering insights for developing (S)-equol-producing EcN probiotics tailored to the gut environment.
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