Metabolic regulation in solventogenic clostridia: regulators, mechanisms and engineering

Yang, Yunpeng; Nie, Xiaoqun; Jiang, Yuqian; Yang, Chen; Gu, Yang; Jiang, Weihong

doi:10.1016/j.biotechadv.2018.02.012

Cited by 34 publications

(30 citation statements)

References 107 publications

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“…C. acetobutylicum has a high amylase activity, being able to metabolize a variety of carbohydrates, such as starch, glucose, and sucrose [69,70]. Recent studies point out the potential use of C. acetobutylicum for the conversion of algal hydrolysates, algae biomass, and galactose into value-added bioproducts [71].…”

Section: Clostridium Acetobutylicummentioning

confidence: 99%

“…Recent studies point out the potential use of C. acetobutylicum for the conversion of algal hydrolysates, algae biomass, and galactose into value-added bioproducts [71]. However, C. acetobutylicum is less effective for complex carbon sources, i.e., lignocellulosic hydrolysates, which may contain toxic substances derived from the dehydration of sugars and aromatics from lignin that are generated during biomass pretreatment [70].…”

Section: Clostridium Acetobutylicummentioning

confidence: 99%

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Clostridium sp. as Bio-Catalyst for Fuels and Chemicals Production in a Biorefinery Context

et al. 2019

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Clostridium sp. is a genus of anaerobic bacteria capable of metabolizing several substrates (monoglycerides, diglycerides, glycerol, carbon monoxide, cellulose, and more), into valuable products. Biofuels, such as ethanol and butanol, and several chemicals, such as acetone, 1,3-propanediol, and butyric acid, can be produced by these organisms through fermentation processes. Among the most well-known species, Clostridium carboxidivorans, C. ragsdalei, and C. ljungdahlii can be highlighted for their ability to use gaseous feedstocks (as syngas), obtained from the gasification or pyrolysis of waste material, to produce ethanol and butanol. C. beijerinckii is an important species for the production of isopropanol and butanol, with the advantage of using hydrolysate lignocellulosic material, which is produced in large amounts by first-generation ethanol industries. High yields of 1,3 propanediol by C. butyricum are reported with the use of another by-product from fuel industries, glycerol. In this context, several Clostridium wild species are good candidates to be used as biocatalysts in biochemical or hybrid processes. In this review, literature data showing the technical viability of these processes are presented, evidencing the opportunity to investigate them in a biorefinery context.

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Section: Clostridium Acetobutylicummentioning

confidence: 99%

Section: Clostridium Acetobutylicummentioning

confidence: 99%

Clostridium sp. as Bio-Catalyst for Fuels and Chemicals Production in a Biorefinery Context

et al. 2019

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“…Of note, five genes known to significantly influence the production of solvents in C. acetobutylicum , including a AbrB-coding gene, two histidine kinase-coding genes and two essential genes in the sol operon (4) were found to be significantly upregulated after sr8384 overexpression according to the microarray data (Figure S7A), although the results of RNA hybridization analysis showed no binding activity between sr8384 and the transcripts of these five genes (Figure S7B). Therefore, it can be concluded that sr8384 indirectly activates the expression of these crucial genes, which may contribute to the solvent production in C. acetobutylicum .…”

Section: Resultsmentioning

confidence: 99%

“…To unlock the full potential of solventogenic clostridia in industrial applications, a detailed understanding of metabolic regulation and discovery of more crucial regulatory elements in these anaerobes are necessary. However, to date, this aspect remains minimally explored, and only a limited number of transcription factors from solventogenic clostridia have been identified and subjected to functional analysis (4); in addition, other types of regulatory molecules and modes (e.g., post-transcriptional and post-translational modes) remain largely unexplored. The lack of knowledge regarding these aspects will inevitably increase the difficulty in identifying new targets for strain improvement.…”

Section: Introductionmentioning

confidence: 99%

The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia

Yang

Lang

Zhang

et al. 2019

Preprint

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20Small noncoding RNAs (sncRNAs) are crucial regulatory molecules in organisms and 21 are well known not only for their roles in the control of diverse essential biological 22 processes but also for their value in genetic modification. However, to date, in 23 gram-positive anaerobic solventogenic clostridia (which are a group of important 24 industrial bacteria with exceptional substrate and product diversity), sncRNAs remain 25 minimally explored, leading to a lack of detailed understanding regarding these 26 important molecules and their use as targets for genetic improvement. Here, we 27 performed large-scale phenotypic screens of a transposon-mediated mutant library of 28 Clostridium acetobutylicum, a typical solventogenic clostridial species, and 29 discovered a novel sncRNA (sr8384) that functions as a determinant positive regulator 30 of growth and solvent synthesis. Comparative transcriptomic data combined with 31 genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator 32and controls multiple targets that are associated with crucial biological processes, 33 through direct or indirect interactions. Notably, modulation of the expression level of 34 either sr8384 or its core target genes significantly increased the growth rate, solvent 35 titer and productivity of the cells, indicating the importance of sr8384-mediated 36 regulatory network in C. acetobutylicum. Furthermore, a homolog of sr8384 was 37 discovered and proven to be functional in another important Clostridium species, C. 38 beijerinckii, suggesting the potential broad role of this sncRNA in clostridia. Our 39 work showcases a previously unknown potent and complex role of sncRNAs in 40 clostridia, providing new opportunities for understanding and engineering these 41 3 anaerobes, including pathogenic Clostridium species.42 4 IMPORTANCE 43The discovery of sncRNAs as new resources for functional studies and strain 44 modifications are promising strategies in microorganisms. However, these crucial 45 regulatory molecules have hardly been explored in industrially important 46 solventogenic clostridia. Here, we identified sr8384 as a novel determinant sncRNA 47 controlling cellular performance of solventogenic Clostridium acetobutylicum and 48 performed detailed functional analysis, which is the most in-depth study of sncRNAs 49 in clostridia to date. We reveal the pleiotropic function of sr8384 and its multiple 50 direct and indirect crucial targets, which represents a valuable source for 51 understanding and optimizing this anaerobe. Of note, manipulation of these targets 52 leads to improved cell growth and solvent synthesis. Our findings provide a new 53 perspective for future studies on regulatory sncRNAs in clostridia. 54 5 93 importance of this sncRNA as well as the related gene network in genetic 94 improvement. Furthermore, we also identified a functional sr8384 homolog in C. 95 beijerinckii, another important Clostridium species that is widely used in the 96 fermentation of lignocellulose hydrolysates, indica...

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“…Gas-fermenting Clostridium species, an important group of autotrophic acetogenic bacteria, have received considerable attention for their ability to use CO 2 and/or syngas to produce multiple important bulk chemicals and fuels, showcasing a huge industrial application value (8). These bacteria sequestrate and assimilate CO 2 via the Wood-Ljungdahl (reductive acetyl-CoA) pathway (WLP), the most efficient among the six different pathways known for microbial carbon fixation (9).…”

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confidence: 99%

Interactive Regulation of Formate Dehydrogenase during CO ₂ Fixation in Gas-Fermenting Bacteria

Zhang

Liu

Zhao

et al. 2020

mBio

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Protein lysine acetylation, a prevalent posttranslational modification, regulates numerous crucial biological processes in cells. Nevertheless, how lysine acetylation interacts with other types of regulation to coordinate metabolism remains largely unknown owing to the complexity of the process. Here, using a representative gas-fermenting bacterium, Clostridium ljungdahlii, we revealed a novel regulatory mechanism that employs both the lysine acetylation and transcriptional regulation systems to interactively control CO2 fixation, a key biological process for utilizing this one-carbon gas. A dominant lysine acetyltransferase/deacetylase system, At2/Dat1, was identified and found to regulate FDH1 (formate dehydrogenase responsible for CO2 fixation) activity via a crucial acetylation site (lysine-29). Notably, the global transcription factor CcpA was also shown to be regulated by At2/Dat1; in turn, CcpA could directly control At2 expression, thus indicating an unreported interaction mode between the acetylation system and transcription factors. Moreover, CcpA was observed to negatively regulate FDH1 expression, which, when combined with At2/Dat1, leads to the collaborative regulation of this enzyme. Based on this concept, we reconstructed the regulatory network related to FDH1, realizing significantly increased CO2 utilization by C. ljungdahlii. IMPORTANCE Microbial CO2 fixation and conversion constitute a potential solution to both utilization of greenhouse gas or industrial waste gases and sustainable production of bulk chemicals and fuels. Autotrophic gas-fermenting bacteria play central roles in this bioprocess. This study provides new insights regarding the metabolic regulatory mechanisms underlying CO2 reduction in Clostridium ljungdahlii, a representative gas-fermenting bacterium. A critical formate dehydrogenase (FDH1) responsible for fixing CO2 and a dominant reversible lysine acetylation system, At2/Dat1, were identified. Furthermore, FDH1 was found to be interactively regulated by both the At2/Dat1 system and the global transcriptional factor CcpA, and the two regulatory systems are mutually restricted. Reconstruction of this multilevel metabolic regulatory module led to improved CO2 metabolism by C. ljungdahlii. These findings not only substantively expand our understanding but also provide a potentially useful metabolic engineering strategy for microbial carbon fixation.

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Metabolic regulation in solventogenic clostridia: regulators, mechanisms and engineering

Cited by 34 publications

References 107 publications

Clostridium sp. as Bio-Catalyst for Fuels and Chemicals Production in a Biorefinery Context

Clostridium sp. as Bio-Catalyst for Fuels and Chemicals Production in a Biorefinery Context

The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia

Interactive Regulation of Formate Dehydrogenase during CO ₂ Fixation in Gas-Fermenting Bacteria

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Metabolic regulation in solventogenic clostridia: regulators, mechanisms and engineering

Cited by 34 publications

References 107 publications

Clostridium sp. as Bio-Catalyst for Fuels and Chemicals Production in a Biorefinery Context

Clostridium sp. as Bio-Catalyst for Fuels and Chemicals Production in a Biorefinery Context

The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia

Interactive Regulation of Formate Dehydrogenase during CO 2 Fixation in Gas-Fermenting Bacteria

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Interactive Regulation of Formate Dehydrogenase during CO ₂ Fixation in Gas-Fermenting Bacteria