Control of solvent production by sigma‐54 factor and the transcriptional activator AdhR in <i>Clostridium beijerinckii</i>

Yang, Bin; Nie, Xiaoqun; Gu, Yang; Jiang, Weihong; Yang, Chen

doi:10.1111/1751-7915.13505

Cited by 8 publications

(22 citation statements)

References 46 publications

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“…The strains expressing AdhRΔGAF and AdhRΔGAFΔPAS also exhibited enhanced acetone synthesis, which may be due to indirect regulation of the genes involved in acetone synthesis (36). Combination of AdhR truncation and SigL overexpression could lead to a further increase in solvent production by C. beijerinckii (13).…”

Section: Figmentioning

confidence: 99%

“…However, little is known about the regulatory mechanisms that maintain redox balance in other clostridia, such as C. beijerinckii. In our previous study, the sigma factor 54 (SigL) and the transcriptional activator AdhR were found to control alcohol synthesis in C. beijerinckii (13). 54 is required for transcription of adhA1 and adhA2 genes, encoding alcohol dehydrogenases (ADHs).…”

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confidence: 99%

“…54 is required for transcription of adhA1 and adhA2 genes, encoding alcohol dehydrogenases (ADHs). Both ADHs, which could work together or individually (14), are responsible for NAD(P)H-dependent synthesis of butanol and ethanol (13). AdhR has been identified as an activator of 54 -dependent transcription of adhA1 and adhA2 (13).…”

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confidence: 99%

“…1A), which would be responsible for ATP hydrolysis to drive the formation of the transcriptionally competent open complex. The C-terminal domain contains a helix-turn-helix motif that directs the binding of AdhR to three sites of upstream activator sequences (UAS) located upstream of the adhA1 and adhA2 promoters (13). Moreover, AdhR contains a GAF domain (named for cyclic GMP-specific and stimulated phosphodiesterases, Anabaena adenylate cyclases, and Escherichia coli FhlA) and a PAS (Per, ARNT, and Sim) domain at the N terminus (Fig.…”

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Ferrous-Iron-Activated Transcriptional Factor AdhR Regulates Redox Homeostasis in Clostridium beijerinckii

Yang

Nie

Xiao

et al. 2020

Appl Environ Microbiol

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The AdhR regulatory protein is an activator of σ54-dependent transcription of adhA1 and adhA2 genes, which are required for alcohol synthesis in Clostridium beijerinckii. Here, we identified the signal perceived by AdhR and determined the regulatory mechanism of AdhR activity. By assaying the activity of AdhR in N-terminally truncated forms, a negative control mechanism of AdhR activity was identified in which the central AAA+ domain is subject to repression by the N-terminal GAF and PAS domains. Binding of Fe2+ to the GAF domain was found to relieve intramolecular repression and stimulate the ATPase activity of AdhR, allowing the AdhR to activate transcription. This control mechanism enables AdhR to regulate transcription of adhA1 and adhA2 in response to cellular redox status. The mutants deficient in AdhR or σ54 showed large shifts in intracellular redox state indicated by the NADH/NAD+ ratio under conditions of increased electron availability or oxidative stress. We demonstrated that the Fe2+-activated transcriptional regulator AdhR and σ54 control alcohol synthesis to maintain redox homeostasis in clostridial cells. Expression of N-terminally truncated forms of AdhR resulted in improved solvent production by C. beijerinckii. IMPORTANCE Solventogenic clostridia are anaerobic bacteria that can produce butanol, ethanol, and acetone, which can be used as biofuels or building block chemicals. Here, we show that AdhR, a σ54-dependent transcriptional activator, senses the intracellular redox status and controls alcohol synthesis in Clostridium beijerinckii. AdhR provides a new example of a GAF domain coordinating a mononuclear non-heme iron to sense and transduce the redox signal. Our study reveals a previously unrecognized functional role of σ54 in control of cellular redox balance and provides new insights into redox signaling and regulation in clostridia. Our results reveal AdhR as a novel engineering target for improving solvent production by C. beijerinckii and other solventogenic clostridia.

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Section: Figmentioning

confidence: 99%

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Ferrous-Iron-Activated Transcriptional Factor AdhR Regulates Redox Homeostasis in Clostridium beijerinckii

Yang

Nie

Xiao

et al. 2020

Appl Environ Microbiol

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“…Creating mutants that are resistant to adverse environments Engineering TF is a way to create strains capable of producing organic solvents that are generally toxic to microbes. 65 Regulating the transcription step by manipulating TF is also a feasible method to confer microbes more resistant to adverse situations. 34 Although TF primarily functions in transcription, its influence can be associated with diverse cellular processes via proteins or noncoding RNAs.…”

Section: Application Of Engineered Tfs Constructing Inducible Expressmentioning

confidence: 99%

Transcriptional factor engineering in microbes for industrial biotechnology

Wang

Liang

Xing

et al. 2020

J of Chemical Tech & Biotech

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Transcription can be regulated by controlling the provision of transcriptional factors (TFs), because TFs determine the transcription process by specifying the binding of RNA polymerase holoenzyme on promoters. Manipulations, such as replacing endogenous TFs with mutants obtained through directed evolution (or rational design), and introducing compatible heterogeneous TFs, are effective ways to regulate transcription. Designing artificial TFs with desired properties by following the principles of protein design and reconstructing ancestral TFs with the information gained from a perspective of evolution by multiple sequence alignments of the related TFs, are feasible alternative options. The engineered TFs can be used to create inducible protein expression systems that respond to a specific stimulus. Moreover, the engineered TFs could lead to a transcriptional profile different from that of the wild-type strains. Accordingly, these engineered TFs could be utilized to construct strains resistant to adverse conditions, since the emergence of resistance generally requires global transcriptional changes at the transcriptomic scale. Meanwhile, these engineered TFs can also be employed in the construction of sophisticatedly designed genetic circuits for diverse purposes. In this paper, we reviewed the advances in the above-mentioned aspects.

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