Rex in Clostridium kluyveri is a global redox-sensing transcriptional regulator

Hu, Liejie; Huang, Haiyan; Huang, Yuan; Tao, Fei; Xie, Huijun; Wang, Shuning

doi:10.1016/j.jbiotec.2016.06.024

Cited by 23 publications

(23 citation statements)

References 39 publications

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“…By the same reasoning, and based on observations made in C. acetobutylicum (Ravcheev et al, 2012), we would have expected to find Rex sequences upstream of ldh (lactate dehydrogenase), hydA (hydrogenase) and ptb-buk (phosphotransbutyrylase-butyrate kinase), as was found in other species (Wietzke and Bahl, 2012, Hu et al, 2016), but none were found, even with relaxed algorithm parameters. Nevertheless, contrary to in silico expectations and the observations made in C. acetobutylicum , the C. pasteurianum rex mutant produced more lactate in glycerol fermentation compared to WT (Fig.…”

Section: Discussionmentioning

confidence: 87%

“…This does not appear to be the case here, as the distance of rex and pyrE to the origin are relatively similar with rex being slightly further away from the origin. In C. kluyveri , rex is self-regulated through the agency of a Rex box, repressor site immediately upstream of the structural gene (Hu et al, 2016). Whilst such an operator site was not evident in the C. pasteurianum rex promoter region used to express the complementing copy of rex , a Rex box was found 340 bp upstream of the rex start codon within the upstream CLPA_c28650 gene (genome position 3068768- 3068786).…”

Section: Resultsmentioning

confidence: 99%

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Towards improved butanol production through targeted genetic modification of Clostridium pasteurianum

Schwarz

Grosse-Honebrink

Derecka

et al. 2017

Metabolic Engineering

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Declining fossil fuel reserves, coupled with environmental concerns over their continued extraction and exploitation have led to strenuous efforts to identify renewable routes to energy and fuels. One attractive option is to convert glycerol, a by-product of the biodiesel industry, into n-butanol, an industrially important chemical and potential liquid transportation fuel, using Clostridium pasteurianum. Under certain growth conditions this Clostridium species has been shown to predominantly produce n-butanol, together with ethanol and 1,3-propanediol, when grown on glycerol. Further increases in the yields of n-butanol produced by C. pasteurianum could be accomplished through rational metabolic engineering of the strain. Accordingly, in the current report we have developed and exemplified a robust tool kit for the metabolic engineering of C. pasteurianum and used the system to make the first reported in-frame deletion mutants of pivotal genes involved in solvent production, namely hydA (hydrogenase), rex (Redox response regulator) and dhaBCE (glycerol dehydratase). We were, for the first time in C. pasteurianum, able to eliminate 1,3-propanediol synthesis and demonstrate its production was essential for growth on glycerol as a carbon source. Inactivation of both rex and hydA resulted in increased n-butanol titres, representing the first steps towards improving the utilisation of C. pasteurianum as a chassis for the industrial production of this important chemical.

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Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Towards improved butanol production through targeted genetic modification of Clostridium pasteurianum

Schwarz

Grosse-Honebrink

Derecka

et al. 2017

Metabolic Engineering

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“…We hypothesized that the effects of PrdR and proline on these pathways might be mediated by a regulatory protein that senses the relative concentrations of NAD + and NADH. Rex, a protein found in many bacterial species, including Clostridium species, and whose activity is controlled by the intracellular NAD + /NADH ratio (Brekasis and Paget, ; Gyan et al , ; McLaughlin et al , ; Wang et al , ; Panitz et al , ; Christensen et al , ; Hu et al , ; Nguyen et al , ; Schwarz et al , ; Yang et al , ), was a candidate for such a regulator. We demonstrate here that C. difficile Rex is indeed a direct repressor of several reductive pathways involved in the production of butyrate and that its ability to bind to DNA is stimulated by NAD + and inhibited by NADH.…”

Section: Introductionmentioning

confidence: 99%

Role of the global regulator Rex in control of NAD⁺‐regeneration in Clostridioides (Clostridium) difficile

Bouillaut

Dubois

Francis

et al. 2019

Molecular Microbiology

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For the human pathogen Clostridioides (also known as Clostridium) difficile, the ability to adapt to nutrient availability is critical for its proliferation and production of toxins during infection. Synthesis of the toxins is regulated by the availability of certain carbon sources, fermentation products and amino acids (e.g. proline, cysteine, isoleucine, leucine and valine). The effect of proline is attributable at least in part to its role as an inducer and substrate of D-proline reductase (PR), a Stickland reaction that regenerates NAD + from NADH. Many Clostridium spp. use Stickland metabolism (co-fermentation of pairs of amino acids) to generate ATP and NAD + . Synthesis of PR is activated by PrdR, a prolineresponsive regulatory protein. Here we report that PrdR, in the presence of proline, represses other NAD + -generating pathways, such as the glycine reductase and succinate-acetyl CoA utilization pathways leading to butyrate production, but does so indirectly by affecting the activity of Rex, a global redox-sensing regulator that responds to the NAD + / NADH ratio. Our results indicate that PR activity is the favored mechanism for NAD + regeneration and that both Rex and PrdR influence toxin production. Using the hamster model of C. difficile infection, we revealed the importance of PrdR-regulated Stickland metabolism in the virulence of C. difficile.

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“…12) (133). Rex has been identified and characterized in archaea and eubacteria regardless of their O 2 requirements (154). Overall, Rex is a transcriptional repressor that remains bound to its DNA targets when the NAD + /NADH ratio is sufficiently high.…”

Section: F Sensors Of the Nad + /Nadh Balance: Rexmentioning

confidence: 99%

“…Rex regulons have been identified in several bacteria, highlighting the importance of this protein in the control of redox homeostasis, central metabolism, or hydrogen production, among other processes (207,302). In Clostridium kluyveri, Rex has been described as a global redox-sensing transcriptional regulator (154). In S. aureus, Rex acts as a central regulator of anaerobic metabolism leading to anaerobic NAD + regeneration.…”

Section: Fig 12 Modulation Of Rexmentioning

confidence: 99%

Redox-Based Transcriptional Regulation in Prokaryotes: Revisiting Model Mechanisms

Sevilla

Bes

González

et al. 2019

Antioxidants & Redox Signaling

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Redox-responsive transcriptional regulation is an intricate process as identical signals may be sensed and transduced by different transcription factors, which often interplay with other DNA-binding proteins with or without regulatory activity. Although there is much information about some key regulators, many others remain to be fully characterized due to the instability of their clusters under oxygen. Understanding the mechanisms and the regulatory networks operated by these regulators is essential for the development of future applications in biotechnology and medicine. Antioxid. Redox Signal. 00, 000-000.

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Rex in Clostridium kluyveri is a global redox-sensing transcriptional regulator

Cited by 23 publications

References 39 publications

Towards improved butanol production through targeted genetic modification of Clostridium pasteurianum

Towards improved butanol production through targeted genetic modification of Clostridium pasteurianum

Role of the global regulator Rex in control of NAD⁺‐regeneration in Clostridioides (Clostridium) difficile

Redox-Based Transcriptional Regulation in Prokaryotes: Revisiting Model Mechanisms

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Rex in Clostridium kluyveri is a global redox-sensing transcriptional regulator

Cited by 23 publications

References 39 publications

Towards improved butanol production through targeted genetic modification of Clostridium pasteurianum

Towards improved butanol production through targeted genetic modification of Clostridium pasteurianum

Role of the global regulator Rex in control of NAD+‐regeneration in Clostridioides (Clostridium) difficile

Redox-Based Transcriptional Regulation in Prokaryotes: Revisiting Model Mechanisms

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Role of the global regulator Rex in control of NAD⁺‐regeneration in Clostridioides (Clostridium) difficile