A bacterial spermidine biosynthetic pathway via carboxyaminopropylagmatine.

Spermidine, a ubiquitous polyamine, is known to be required for critical physiological functions in bacteria. Two principal pathways are known for spermidine biosynthesis, both of which involve aminopropylation of putrescine. Here, we identified a spermidine biosynthetic pathway via a previously unknown metabolite, carboxyaminopropylagmatine (CAPA), in a model cyanobacterium sp.

Pleiotropic Regulator GssR Positively Regulates Autotrophic Growth of Gas-Fermenting .

is a representative autotrophic acetogen capable of producing multiple chemicals from one-carbon gases (CO/CO). The metabolic and regulatory networks of this carbon-fixing bacterium are interesting, but still remain minimally explored. Here, based on bioinformatics analysis followed by functional screening, we identified a RpiR family transcription factor (TF) that can regulate the autotrophic growth and carbon fixation of .

Increasing brain N-acetylneuraminic acid alleviates hydrocephalus-induced neurological deficits.

Aims: This metabolomic study aimed to evaluate the role of N-acetylneuraminic acid (Neu5Ac) in the neurological deficits of normal pressure hydrocephalus (NPH) and its potential therapeutic effect.

Methods: We analyzed the metabolic profiles of NPH using cerebrospinal fluid with multivariate and univariate statistical analyses in a set of 42 NPH patients and 38 controls. We further correlated the levels of differential metabolites with severity-related clinical parameters, including the normal pressure hydrocephalus grading scale (NPHGS).

Functional dissection and modulation of the BirA protein for improved autotrophic growth of gas-fermenting Clostridium ljungdahlii.

Gas-fermenting Clostridium species can convert one-carbon gases (CO /CO) into a variety of chemicals and fuels, showing excellent application prospects in green biological manufacturing. The discovery of crucial genes and proteins with novel functions is important for understanding and further optimization of these autotrophic bacteria. Here, we report that the Clostridium ljungdahlii BirA protein (ClBirA) plays a pleiotropic regulator role, which, together with its biotin protein ligase (BPL) activity, enables an effective control of autotrophic growth of C.

Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence.

Host-derived fatty acids are an important carbon source for pathogenic mycobacteria during infection. How mycobacterial cells regulate the catabolism of fatty acids to serve the pathogenicity, however, remains unknown. Here, we identified a TetR-family transcriptional factor, FdmR, as the key regulator of fatty acid catabolism in the pathogen by combining use of transcriptomics, chromatin immunoprecipitation followed by sequencing, dynamic C-based flux analysis, metabolomics, and lipidomics.

Ferrous-Iron-Activated Transcriptional Factor AdhR Regulates Redox Homeostasis in .

The AdhR regulatory protein is an activator of σ-dependent transcription of and genes, which are required for alcohol synthesis in 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 Fe to the GAF domain was found to relieve intramolecular repression and stimulate the ATPase activity of AdhR, allowing the AdhR to activate transcription.

Control of solvent production by sigma-54 factor and the transcriptional activator AdhR in Clostridium beijerinckii.

Clostridia are obligate anaerobic bacteria that can produce solvents such as acetone, butanol and ethanol. Alcohol dehydrogenases (ADHs) play a key role in solvent production; however, their regulatory mechanisms remain largely unknown. In this study, we characterized the regulatory mechanisms of two ADH-encoding genes in C.

Biological insights into non-model microbial hosts through stable-isotope metabolic flux analysis.

Stable-isotope metabolic flux analysis is an important approach to unravel the metabolic network and its regulation in organisms. It has become a key analytical technology for biotechnological applications. During recent years non-model microorganisms have received increasing attention because they possess unique metabolic capabilities and can serve as a host for production of biofuels and biochemicals.

Genomic reconstruction of σ regulons in Clostridiales.

Background: The σ factor controls unique promoters and interacts with a specialized activator (enhancer binding proteins [EBP]) for transcription initiation. Although σ is present in many Clostridiales species that have great importance in human health and biotechnological applications, the cellular processes controlled by σ remain unknown.

Results: For systematic analysis of the regulatory functions of σ, we performed comparative genomic reconstruction of transcriptional regulons of σ in 57 species from the Clostridiales order.

The cyanobacterial ornithine-ammonia cycle involves an arginine dihydrolase.

Living organisms have evolved mechanisms for adjusting their metabolism to adapt to environmental nutrient availability. Terrestrial animals utilize the ornithine-urea cycle to dispose of excess nitrogen derived from dietary protein. Here, we identified an active ornithine-ammonia cycle (OAC) in cyanobacteria through an approach combining dynamic N and C tracers, metabolomics, and mathematical modeling.

Metabolic regulation in solventogenic clostridia: regulators, mechanisms and engineering.

Solventogenic clostridia, a group of important industrial microorganisms, have exceptional substrate and product diversity, capable of producing a series of two-carbon and even long-chain chemicals and fuels by using various substrates, including sugars, cellulose and hemicellulose, and C1 gases. For the sake of in-depth understanding and engineering these anaerobic microorganisms for broader applications, studies on metabolic regulation of solventogenic clostridia had been extensively carried out during the past ten years, based on the rapid development of various genetic tools. To date, a number of regulators that are essential for cell physiological and metabolic processes have been identified in clostridia, and the relevant mechanisms have also been dissected, providing a wealth of valuable information for metabolic engineering.

PTS regulation domain-containing transcriptional activator CelR and sigma factor σ(54) control cellobiose utilization in Clostridium acetobutylicum.

The phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulation domain (PRD)-containing enhancer binding proteins (EBPs) are an important class of σ(54) -interacting transcriptional activators. Although PRD-containing EBPs are present in many Firmicutes, most of their regulatory functions remain unclear. In this study, the transcriptional regulons of about 50 PRD-containing EBPs in diverse Firmicutes species are reconstructed by using a comparative genomic approach, which contain the genes associated with utilization of β-glucosides, fructose/levan, mannose/glucose, pentitols, and glucosamine/fructosamine.

Redox-responsive repressor Rex modulates alcohol production and oxidative stress tolerance in Clostridium acetobutylicum.

Rex, a transcriptional repressor that modulates its DNA-binding activity in response to NADH/NAD(+) ratio, has recently been found to play a role in the solventogenic shift of Clostridium acetobutylicum. Here, we combined a comparative genomic reconstruction of Rex regulons in 11 diverse clostridial species with detailed experimental characterization of Rex-mediated regulation in C. acetobutylicum.