High Titer of (<i>S</i>)-Equol Synthesis from Daidzein in <i>Escherichia coli</i>

Deng, Hanning; Gao, Song; Zhang, Weiping; Zhang, Tianmeng; Li, Ning; Zhou, Jingwen

doi:10.1021/acssynbio.2c00378

Cited by 7 publications

(9 citation statements)

References 60 publications

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“… Li F. et al (2022) led to a further 19% increase in glucoamylase activity by overexpressing mitochondrial NADH kinase (AN17) and malic enzyme (MaeA). Deng et al (2022) optimized a cascade system by regulating the intensity of NADPH gene expression to produce a higher (S)-equol titer (3418.5 mg/L) with a conversion rate of approximately 85.9%. van Aalst et al (2022) functional expression of the gene in anaerobic, slow-growing chemostat cultivation on glucose-sorbitol mixtures resulted in a 12-fold higher co-consumption rate of sorbitol than that observed in sorbitol-consuming reference strains.…”

Section: Regulation Of Cofactor Metabolic Balance and Its Applicationmentioning

confidence: 99%

Application of cofactors in the regulation of microbial metabolism: A state of the art review

Sun

Zhang

et al. 2023

Front. Microbiol.

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Cofactors are crucial chemicals that maintain cellular redox balance and drive the cell to do synthetic and catabolic reactions. They are involved in practically all enzymatic activities that occur in live cells. It has been a hot research topic in recent years to manage their concentrations and forms in microbial cells by using appropriate techniques to obtain more high-quality target products. In this review, we first summarize the physiological functions of common cofactors, and give a brief overview of common cofactors acetyl coenzyme A, NAD(P)H/NAD(P)+, and ATP/ADP; then we provide a detailed introduction of intracellular cofactor regeneration pathways, review the regulation of cofactor forms and concentrations by molecular biological means, and review the existing regulatory strategies of microbial cellular cofactors and their application progress, to maximize and rapidly direct the metabolic flux to target metabolites. Finally, we speculate on the future of cofactor engineering applications in cell factories. Graphical Abstract

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Section: Regulation Of Cofactor Metabolic Balance and Its Applicationmentioning

confidence: 99%

Application of cofactors in the regulation of microbial metabolism: A state of the art review

Sun

Zhang

et al. 2023

Front. Microbiol.

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“…Fecal transplant therapy has demonstrated success in conferring an ( S )-equol-producing phenotype in hosts by providing them with exogenous gut bacteria expressing the necessary enzymes for daidzein conversion into ( S )-equol [ 6 , 7 ]. Recently, engineered bacteria-integrated ( S )-equol-producing pathways have been utilized as efficient whole-cell biocatalysts for ( S )-equol production [ 3 , 8 ]. Given that EcN is a probiotic widely used as a host for the development of engineered probiotics [ 9 , 10 ], it can be used to develop an engineered probiotic with the capability of converting dietary isoflavones into ( S )-equol efficiently [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…The subsequent reduction of ( S )-dihydrodaidzein to t -tetrahydrodaidzein occurs through dihydrodaidzein reductase (DHDR), followed by the transformation of t -tetrahydrodaidzein into ( S )-equol via tetrahydrodaidzein reductase (THDR) [ 5 ]. Notably, the enzymes DZNR and DHDR belong to the category of NADPH-dependent oxidoreductases, and the biosynthesis of 1 mol of ( S )-equol necessitates the consumption of 2 mol of NADPH [ 8 , 12 ]. Therefore, the conversion of daidzein to ( S )-equol will be impaired when intracellular NADPH is insufficient [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Deciphering the Crucial Roles of the Quorum-Sensing Transcription Factor SdiA in NADPH Metabolism and (S)-Equol Production in Escherichia coli Nissle 1917

Wang,

Dai,

Azi

et al. 2024

Antioxidants

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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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“…However, most ( S )-equol-producing natural isolate strains grow at a relatively low rate under strictly anaerobic conditions . Currently, the development of microbial cell factories through introducing an ( S )-equol biosynthetic pathway into microbes has emerged as a sustainable and eco-friendly alternative for large-scale ( S )-equol production. ,− …”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of (S)-Equol from Soy Whey by Metabolically Engineered Escherichia coli

Zhe

Azi

et al. 2023

J. Agric. Food Chem.

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(S)-Equol is one of the most bioactive metabolites of the isoflavones with immense nutritional and pharmaceutical value. Soy whey is the major liquid byproduct of the soy product processing industries that is rich in nutrients and (S)-equol biosynthetic precursor daidzin. However, it is usually disposed into the sewage, causing high environmental contamination. Herein, we constructed a recombinant Escherichia coli for the biosynthesis of (S)-equol from soy whey. First, we evaluated daidzin-specific transporters and optimized the anaerobically induced P nar in the (S)-equol biosynthesis cassette to produce (S)-equol from daidzin. Then, sucrase and α-galactosidase were co-expressed to confer sucrose, stachyose, and raffinose utilization capacity on E. coli. Meanwhile, EIIBCAglc was inactivated to eliminate the daidzin transport inhibition induced by glucose. Finally, combining these strategies and optimizing the fermentation conditions, the optimal strain produced 91.5 mg/L of (S)-equol with a yield of 0.96 mol/mol substrates in concentrated soy whey. Overall, this new strategy is an attractive route to broaden the applications of soy whey and achieve the eco-friendly production of (S)-equol.

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High Titer of (S)-Equol Synthesis from Daidzein in Escherichia coli

Cited by 7 publications

References 60 publications

Application of cofactors in the regulation of microbial metabolism: A state of the art review

Application of cofactors in the regulation of microbial metabolism: A state of the art review

Deciphering the Crucial Roles of the Quorum-Sensing Transcription Factor SdiA in NADPH Metabolism and (S)-Equol Production in Escherichia coli Nissle 1917

Biosynthesis of (S)-Equol from Soy Whey by Metabolically Engineered Escherichia coli

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