Engineering <i>Escherichia coli</i> for Conversion of Dietary Isoflavones in the Gut

Kydd, LeNaiya; Shiveshwarkar, Priyanka; Jaworski, Justyn

doi:10.1021/acssynbio.2c00277

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…Recently, Kydd et al developed a successful equol bioengineering approach with a proof-of-concept in vivo . 135 They produced E. coli Nissle strains with ectopic expression of the genes required for daidzein-to-equol conversion (DZNR, DDRC, DHDR, and THDR) cloned from the Lactococcus garvieae 20–92 strain mentioned above. 62 These four genes were split into two complementary E. coli Nissle P1 and P2 strains to obtain a higher product yield.…”

Section: Development and Clinical Testing Of Novel Substrate–microbe ...mentioning

confidence: 99%

Exploring substrate–microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions

Speckmann,

Ehring,

et al. 2024

Gut Microbes

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Gut microbiota is an important modulator of human health and contributes to high inter-individual variation in response to food and pharmaceutical ingredients. The clinical outcomes of interventions with prebiotics, probiotics, and synbiotics have been mixed and often unpredictable, arguing for novel approaches for developing microbiome-targeted therapeutics. Here, we review how the gut microbiota determines the fate of and individual responses to dietary and xenobiotic compounds via its immense metabolic potential. We highlight that microbial metabolites play a crucial role as targetable mediators in the microbiota-host health relationship. With this in mind, we expand the concept of synbiotics beyond prebiotics’ role in facilitating growth and engraftment of probiotics, by focusing on microbial metabolism as a vital mode of action thereof. Consequently, we discuss synbiotic compositions that enable the guided metabolism of dietary or co-formulated ingredients by specific microbes leading to target molecules with beneficial functions. A workflow to develop novel synbiotics is presented, including the selection of promising target metabolites (e.g. equol, urolithin A, spermidine, indole-3 derivatives), identification of suitable substrates and producer strains applying bioinformatic tools, gut models, and eventually human trials. In conclusion, we propose that discovering and enabling specific substrate–microbe interactions is a valuable strategy to rationally design synbiotics that could establish a new category of hybrid nutra-/pharmaceuticals.

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Section: Development and Clinical Testing Of Novel Substrate–microbe ...mentioning

confidence: 99%

Exploring substrate–microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions

Speckmann,

Ehring,

et al. 2024

Gut Microbes

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“…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%

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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Engineering Escherichia coli for Conversion of Dietary Isoflavones in the Gut

Cited by 2 publications

References 33 publications

Exploring substrate–microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions

Exploring substrate–microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions

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

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