Metabolomics-driven discovery of therapeutic targets for cancer cachexia.

Cancer cachexia (CC) is a devastating metabolic syndrome characterized by skeletal muscle wasting and body weight loss, posing a significant burden on the health and survival of cancer patients. Despite ongoing efforts, effective treatments for CC are still lacking. Metabolomics, an advanced omics technique, offers a comprehensive analysis of small-molecule metabolites involved in cellular metabolism. In CC research, metabolomics has emerged as a valuable tool for identifying diagnostic biomarkers, unravelling molecular mechanisms and discovering potential therapeutic targets. A comprehensive search strategy was implemented to retrieve relevant articles from primary databases, including Web of Science, Google Scholar, Scopus and PubMed, for CC and metabolomics. Recent advancements in metabolomics have deepened our understanding of CC by uncovering key metabolic signatures and elucidating underlying mechanisms. By targeting crucial metabolic pathways including glucose metabolism, amino acid metabolism, fatty acid metabolism, bile acid metabolism, ketone body metabolism, steroid metabolism and mitochondrial energy metabolism, it becomes possible to restore metabolic balance and alleviate CC symptoms. This review provides a comprehensive summary of metabolomics studies in CC, focusing on the discovery of potential therapeutic targets and the evaluation of modulating specific metabolic pathways for CC treatment. By harnessing the insights derived from metabolomics, novel interventions for CC can be developed, leading to improved patient outcomes and enhanced quality of life.

Metabolism of Inulin via Difructose Anhydride I Pathway in Microbacterium flavum.

Difructose anhydride I (DFA-I) can be produced from inulin, with DFA-I-forming inulin fructotransferase (IFTase-I). However, the metabolism of inulin through DFA-I remains unclear. To clarify this pathway, several genes of enzymes related to this pathway in the genome of Microbacterium flavum DSM 18909 were synthesized, and the corresponding enzymes were encoded, purified, and investigated in vitro. After inulin is decomposed to DFA-I by IFTase-I, DFA-I is hydrolyzed to inulobiose by DFA-I hydrolase. Inulobiose is then hydrolyzed by ß-fructofuranosidase to form fructose. Finally, fructose enters glycolysis through fructokinase. A ß-fructofuranosidase (MfFFase1) clears the byproducts (sucrose and fructo-oligosaccharides), which might be partially hydrolyzed by fructan ß-(2,1)-fructosidase/1-exohydrolase and another fructofuranosidase (MfFFase2). Exploring the DFA-I pathway of inulin and well-studied enzymes in vitro extends our basic scientific knowledge of the energy-providing way of inulin, thereby paving the way for further investigations in vivo and offering a reference for further nutritional investigation of inulin and DFA-I in the future.

[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.

Raman-AFM-fluorescence-guided impact of linoleic and eicosapentaenoic acids on subcellular structure and chemical composition of normal and cancer human colon cells.

The regular overconsumption of high-energy food (rich in lipids and sugars) results in elevated nutrient absorption in intestine and consequently excessive accumulation of lipids in many organs e.g.: liver, adipose tissue, muscles. In the long term this can lead to obesity and obesity-associated diseases e.g. type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease, inflammatory bowel disease (IBD). In the presented paper based on RI data we have proved that Raman maps can be used successfully for subcellular structures visualization and analysis of fatty acids impact on morphology and chemical composition of human colon single cells - normal and cancer. Based on Raman data we have investigated the changes related to endoplasmic reticulum, mitochondria, lipid droplets and nucleus. Analysis of ratios calculated based on Raman bands typical for proteins (1256, 1656 cm-1), lipids (1304, 1444 cm-1) and nucleic acids (750 cm-1) has confirmed for endoplasmic reticulum the increased activity of this organelle in lipoproteins synthesis upon FAs supplementation; for LDs the changes of desaturation of accumulated lipids with the highest unsaturation level for CaCo-2 cells upon EPA supplementation; for mitochondria the stronger effect of FAs supplementation was observed for CaCo-2 cells confirming the increased activity of this organelle responsible for energy production necessary for tumor development; the weakest impact of FAs supplementation was observed for nucleus for both types of cells and both types of acids. Fluorescence imaging was used for the investigations of changes in LDs/ER morphology. Our measurements have shown the increased area of LDs/ER for CaCo-2 cancer cells, and the strongest effect was noticed for CaCo-2 cells upon EPA supplementation. The increased participation of lipid structures for all types of cells upon FAs supplementation has been confirmed also by AFM studies. The lowest YM values have been observed for CaCo-2 cells including samples treated with FAs.

Isolation and characterization of novel 3,3'-iminodipropionitrile biodegrading Paracoccus communis, from an industrial wastewater treatment bioreactor.

Until now, bacteria able to degrade, 3,3'-iminodipropionitrile (IDPN), a neurotoxin that destroys vestibular hair cells, causing ototoxicity, culminating in irreversible movement disorders, had never been isolated. The aim of this study was to isolate a novel IDPN-biodegrading microorganism and characterize its metabolic pathway. Enrichment was performed by inoculating activated sludge from a wastewater treatment bioreactor that treated IDPN-contaminated wastewater in M9 salt medium, with IDPN as the sole carbon source. A bacterial strain with a spherical morphology that could grow at high concentrations was isolated on a solid medium. Growth of the isolated strain followed the Monod kinetic model. Based on the 16S rRNA gene, the isolate was Paracoccus communis. Whole-genome sequencing revealed that the isolated P. communis possessed the expected full metabolic pathway for IDPN biodegradation. Transcriptome analyses confirmed the overexpression of the gene encoding hydantoinase/oxoprolinase during the exponential growth phase under IDPN-fed conditions, suggesting that the enzyme involved in cleaving the imine bond of IDPN may promote IDPN biodegradation. Additionally, the newly discovered P. communis isolate seems to metabolize IDPN through cleavage of the imine bond in IDPN via nitrilase, nitrile hydratase, and amidase reactions. Overall, this study lays the foundation for the application of IDPN-metabolizing bacteria in the remediation of IDPN-contaminated environments.

Nitrogen and sulfur cycling and their coupling mechanisms in eutrophic lake sediment microbiomes.

Microorganisms play important roles in the biogeochemical cycles of lake sediment. However, the integrated metabolic mechanisms governing nitrogen (N) and sulfur (S) cycling in eutrophic lakes remain poorly understood. Here, metagenomic analysis of field and bioreactor enriched sediment samples from a typical eutrophic lake were applied to elucidate the metabolic coupling of N and S cycling. Our results showed significant diverse genes involved in the pathways of dissimilatory sulfur metabolism, denitrification and dissimilatory nitrate reduction to ammonium (DNRA). The N and S associated functional genes and microbial groups generally showed significant correlation with the concentrations of NH4+, NO2- and SO42, while with relatively low effects from other environmental factors. The gene-based co-occurrence network indicated clear cooperative interactions between N and S cycling in the sediment. Additionally, our analysis identified key metabolic processes, including the coupled dissimilatory sulfur oxidation (DSO) and DNRA as well as the association of thiosulfate oxidation complex (SOX systems) with denitrification pathway. However, the enriched N removal microorganisms in the bioreactor ecosystem demonstrated an additional electron donor, incorporating both the SOX systems and DSO processes. Metagenome-assembled genomes-based ecological model indicated that carbohydrate metabolism is the key linking factor for the coupling of N and S cycling. Our findings uncover the coupling mechanisms of microbial N and S metabolism, involving both inorganic and organic respiration pathways in lake sediment. This study will enhance our understanding of coupled biogeochemical cycles in lake ecosystems.

Application of multiple strategies to enhance oleanolic acid biosynthesis by engineered Saccharomyces cerevisiae.

Oleanolic acid and its derivatives are widely used in the pharmaceutical, agricultural, cosmetic and food industries. Previous studies have shown that oleanolic acid production levels in engineered cell factories are low, which is why oleanolic acid is still widely extracted from traditional medicinal plants. To construct a highly efficient oleanolic acid production strain, rate-limiting steps were regulated by inducible promoters and the expression of key genes in the oleanolic acid synthetic pathway was enhanced. Subsequently, precursor pool expansion, pathway refactoring and diploid construction were considered to harmonize cell growth and oleanolic acid production. The multi-strategy combination promoted oleanolic acid production of up to 4.07 g/L in a 100 L bioreactor, which was the highest level reported.

Potential mechanisms of propionate degradation and methanogenesis in anaerobic digestion coupled with microbial electrolysis cell system: Importance of biocathode.

Microbial electrolysis cells (MEC) have the potential for enhancing the efficiency of anaerobic digestion (AD). In this study, microbiological and metabolic pathways in the biocathode of anaerobic digestion coupled with microbial electrolysis cells system (AD-MEC) were revealed to separate bioanode. The biocathode efficiently degraded 90 % propionate within 48 h, leading to a methane production rate of 3222 mL·m-2·d-1. The protein and heme-rich cathodic biofilm enhanced redox capacity and facilitated interspecies electron transfer. Key acid-degrading bacteria, including Dechloromonas agitata, Ignavibacteriales bacterium UTCHB2, and Syntrophobacter fumaroxidans, along with functional proteins such as cytochrome c and e-pili, established mutualistic relationships with Methanothrix soehngenii. This synergy facilitated a multi-pathway metabolic process that converted acetate and CO2 into methane. The study sheds light on the intricate microbial dynamics within the biocathode, suggesting promising prospects for the scalable integration of AD-MEC and its potential in sustainable energy production.

Caproicibacter sp. BJN0012, a potential new species isolated from cellar mud for caproic acid production from glucose.

Acids play a crucial role in enhancing the flavor of strong-aroma Baijiu, and among them, caproic acid holds significant importance in determining the flavor of the final product. However, the metabolic synthesis of caproic acid during the production process of Baijiu has received limited attention, resulting in fluctuations in caproic acid content among fermentation batches and generating production instability. Acid-producing bacteria found in the cellar mud are the primary microorganisms responsible for caproic acid synthesis, but there is a lack of research on the related microbial resources and their metabolic properties. Therefore, it is essential to identify and investigate these acid-producing microorganisms from cellar mud to ensure stable caproic acid synthesis. In this study, a unique strain was isolated from the cellar mud, exhibiting a 98.12 % similarity in its 16 S rRNA sequence and an average nucleotide identity of 79.57 % with the reference specie, together with the DNA-DNA hybridization of 23.20 % similarity, confirming the distinct species boundaries. The strain was able to produce 1.22 ± 0.55 g/L caproic acid from glucose. Through genome sequencing, annotation, and bioinformatics analysis, the complete pathway of caproic acid synthesis from glucose was elucidated, and the catalytic mechanism of the key thiolase for caproic acid synthesis was investigated. These findings provide useful fundamental data for revealing the metabolic properties of caproic acid-producing bacteria found in cellar mud.

Corrigendum: Comprehensive transcriptomic analysis of critical RNA regulation associated with metabolism and prognosis in clear cell renal carcinoma.

[This corrects the article DOI: 10.3389/fcell.2021.709490.].

Predicting The Pathway Involvement Of Metabolites Based on Combined Metabolite and Pathway Features.

A major limitation of most metabolomics datasets is the sparsity of pathway annotations of detected metabolites. It is common for less than half of identified metabolites in these datasets to have known metabolic pathway involvement. Trying to address this limitation, machine learning models have been developed to predict the association of a metabolite with a "pathway category", as defined by one of the metabolic knowledgebases like the Kyoto Encyclopedia of Gene and Genomes. Most of these models are implemented as a single binary classifier specific to a single pathway category, requiring a set of binary classifiers for generating predictions for multiple pathway categories. This single binary classifier per pathway category approach both multiplies the computational resources necessary for training while diluting the positive entries in gold standard datasets needed for training. To address the limitations of training separate classifiers, we propose a generalization of the metabolic pathway prediction problem using a single binary classifier that accepts both features representing a metabolite and features representing a generic pathway category and then predicts whether the given metabolite is involved in the corresponding pathway category. We demonstrate that this metabolite-pathway features-pair approach is not only competitive with the combined performance of training separate binary classifiers, but it outperforms the previous benchmark models.

Phytochemical diversity and their adaptations to abiotic and biotic pressures in fine roots across a climatic gradient.

Phytochemicals and their ecological significance are long ignored in trait-based ecology. Moreover, the adaptations of phytochemicals produced by fine roots to abiotic and biotic pressures are less understood. Here, we explored the fine roots metabolomes of 315 tree species and their rhizosphere microbiome in southwestern China spanning tropical, subtropical, and subalpine forest ecosystems, to explore phytochemical diversity and endemism patterns of various metabolic pathways and phytochemical-microorganism interactions. We found that subalpine species showed higher phytochemical diversity but lower interspecific variation than tropical species, which favors coping with high abiotic pressures. Tropical species harbored higher interspecific phytochemical variation and phytochemical endemism, which favors greater species coexistence and adaptation to complex biotic pressures. Moreover, there was evidence of widespread chemical niche partitioning of closely related species in all regions, and phytochemicals showed a weak phylogenetic signal, but were regulated by abiotic and biotic pressures. Our findings support the Latitudinal Biotic Interaction Hypothesis, i.e., the intensity of phytochemical-microorganism interactions decreases from tropical to subalpine regions, which promotes greater microbial community turnover and phytochemical niche partitioning of host plants in the tropics than in higher latitude forests. Our study reveals the convergent phytochemical diversity patterns of various pathways and their interactions with microorganism, thus promoting species coexistence.

Potential Mechanisms of Casein Hexapeptide YPVEPF on Stress-Induced Anxiety and Insomnia Mice and Its Molecular Effects and Key Active Structure.

The hexapeptide YPVEPF with strong sleep-enhancing effects could be detected in rat brain after a single oral administration as we previously proved. In this study, the mechanism and molecular effects of YPVEPF in the targeted stress-induced anxiety mice were first investigated, and its key active structure was further explored. The results showed that YPVEPF could significantly prolong sleep duration and improve the anxiety indexes, including prolonging the time spent in the open arms and in the center. Meanwhile, YPVEPF showed strong sleep-enhancing effects by significantly increasing the level of the GABA/Glu ratio, 5-HT, and dopamine in brain and serum and regulating the anabolism of multiple targets, but the effects could be blocked by bicuculline and WAY100135. Moreover, the molecular simulation results showed that YPVEPF could stably bind to the vital GABAA and 5-HT1A receptors due to the vital structure of Tyr-Pro-Xaa-Xaa-Pro-, and the electrostatic and van der Waals energy played dominant roles in stabilizing the conformation. Therefore, YPVEPF displayed sleep-enhancing and anxiolytic effects by regulating the GABA-Glu metabolic pathway and serotoninergic system depending on distinctive self-folding structures with Tyr and two Pro repeats.

Research overview on the genetic mechanism underlying the biosynthesis of polysaccharide in tuber plants.

Tuber plants are of great significance in the world as human food crops. Polysaccharides, important metabolites in tuber plants, also serve as a source of innovative drugs with significant pharmacological effects. These drugs are particularly known for their immunomodulation and antitumor properties. To fully exploit the potential value of tuber plant polysaccharides and establish a synthetic system for their targeted synthesis, it is crucial to dissect their metabolic processes and genetic regulatory mechanisms. In this article, we provide a comprehensive summary of the basic pathways involved in the synthesis of various types of tuber plant polysaccharides. We also outline the key research progress that has been made in this area in recent years. We classify the main types and functions of tuber plant polysaccharides and analyze the biosynthetic processes and genetic regulation mechanisms of key enzymes involved in the metabolic pathways of starch, cellulose, pectin, and fructan in tuber plants. We have identified hexokinase and glycosyltransferase as the key enzymes involved in the polysaccharide synthesis process. By elucidating the synthesis pathway of polysaccharides in tuber plants and understanding the underlying mechanism of action of key enzymes in the metabolic pathway, we can provide a theoretical framework for enhancing the yield of polysaccharides and other metabolites in plant culture cells. This will ultimately lead to increased production efficiency.

Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation.

The environmental behavior of and risks associated with nanoplastics (NPs) have attracted considerable attention. However, compared to pristine NPs, environmental factors such as ultraviolet (UV) irradiation that lead to changes in the toxicity of NPs have rarely been studied. We evaluated the changes in morphology and physicochemical properties of polystyrene (PS) NPs before and after UV irradiation, and compared their hepatotoxicity in mice. The results showed that UV irradiation caused particle size reduction and increased the carbonyl index (CI) and negative charge on the particle surface. UV-aged PS NPs (aPS NPs) could induce the generation of hydroxyl radicals (·OH), but also further promoted the generation of ·OH in the Fenton reaction system. Hepatic pathological damage was more severe in mice exposed to aPS NPs, accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein, alanine aminotransferase and aspartate aminotransferase levels. In addition, exposure to PS NPs and aPS NPs, especially aPS NPs, triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver. Compared with PS NPs, exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways, especially glutathione metabolism. Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of ·OH, enhancing PS NPs-induced liver damage and metabolic disorders. This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer.

INTRODUCTION: Baicalein, a bioactive component of Scutellaria baicalensis Georgi, has been shown to promote apoptosis in non-small cell lung cancer cells. However, previous studies have not determined if baicalein exerts proapoptotic effects by modulating the metabolic pathways. OBJECTIVE: To investigate if baicalein induces apoptosis in lung cancer cells by modulating the glutamine-mTOR metabolic pathway. METHODS: The in vivo anti-lung cancer activity of baicalein (50, 100, and 200 mg/kg) was evaluated using a xenograft model. In vitro experiments were used to assess the efficacy of baicalein (for H1299: 12.5, 25, and 50 µM; for A549: 10, 20, and 40 µM) on lung cancer cell proliferation, colony formation, and apoptosis. Metabolomics analysis was performed using liquid chromatography-mass spectrometry. The binding of baicalein to glutamine transporters and glutaminase was examined using molecular docking. The overexpression of glutamine transporters was validated using qRT-PCR and western blot analyses. The levels of ASCT2, LAT1, GLS1, p-mTOR, mTOR, and apoptosis-related proteins were evaluated using western blot analysis. RESULTS: Baicalein inhibited lung cancer xenograft tumor growth in vivo and suppressed proliferation and promoted apoptosis in lung cancer cells in vitro. Additionally, baicalein altered amino acid metabolites, especially glutamine metabolites, in H1299 and A549 cells. Mechanistically, baicalein interacted with glutamine transporters as well as glutaminase and inhibited their activation. The expression of mTOR, an apoptosis-related protein and downstream target of glutamine metabolism, was also inhibited by baicalein treatment. Importantly, we next demonstrated the suppression of mTOR signaling and the induction of apoptosis by baicalein were achieved by regulating glutamine metabolism. CONCLUSION: Baicalein inhibited the mTOR signaling pathway and induced apoptosis by downregulating glutamine metabolism. The potential of baicalein to induce apoptosis in lung cancer cells by selectively targeting the glutamine-mTOR pathway suggests an encouraging approach for treating lung cancer.

Differential Characteristics of the Metabolic Profiles and Microbial Community between Superior and Normal Grades of Nongxiangxing-daqu.

Nongxiangxing-daqu (NXDQ), as a saccharification and fermentation agent, directly affects the flavor and yield of fresh Nongxiangxing Baijiu (NXBJ). The difference in fermentation temperature owing to the artificial turning operation leads to the formation of superior (S) and normal (N) grades of NXDQ. Here, aiming to explore the discriminant characteristics of two grades of NXDQ, we studied the physicochemical properties, volatile compounds and microbial communities using HS-SPME-GC/MS and high-throughput sequencing technology. The NXDQ grades presented different physicochemical properties. Staphylococcus, Weissella, Lactobacillus and Thermoascus were dominant in the S grade (S-NXDQ), while Bacillus, Thermoactinomyces and Aspergillus were predominant in the N grade (N-NXDQ). Higher alcohols, aldehydes and ketones positively correlated with the bacterial biomarkers could be used as metabolic biomarkers for N-NXDQ; the S-NXDQ had a higher abundance of key enzymes involved in lactic acid and ethanol fermentation, while N-NXDQ had a higher abundance of key enzymes involved in amino acid synthesis and long-chain fatty acid and lipid metabolism. N-NXDQ and S-NXDQ had different microbial and metabolic biomarkers. These findings provide insight into the discriminant characteristics of different grades of NXDQ, a theoretical basis for rational evaluation of NXDQ, and effective information for quality improvement of daqu.

Changes in the Serum Metabolome in an Inflammatory Model of Osteoarthritis in Rats.

Osteoarthritis (OA) is a pathology of great impact worldwide. Its physiopathology is not completely known, and it is usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. This study was performed on thirty rats. OA was induced in all animals by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction and 28, 56, and 84 days following induction. Histological evaluation confirmed OA in all samples. The results of this study allow the identification of several changes in 18 metabolites over time, including organic acids, benzenoids, heterocyclic compounds, and lipids after 28 days, organic acids after 56 days, and lipid classes after 84 days. We conclude that OA induces serological changes in the serum metabolome, which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.

Greenhouse gas emission characteristics during kitchen waste composting with biochar and zeolite addition.

Aerobic kitchen waste composting can contribute to greenhouse gas (GHGs) emissions and global warming. This study investigated the effects of biochar and zeolite on GHGs emissions during composting. The findings demonstrated that biochar could reduce N2O and CH4 cumulative releases by 47.7 %and 47.9 %, respectively, and zeolite could reduce the cumulative release of CO2 by 28.4 %. Meanwhile, the biochar and zeolite addition could reduce the abundance of potential core microorganisms associated with GHGs emissions. In addition, biochar and zeolite reduced N2O emissions by regulating the abundance of nitrogen conversion functional genes. Biochar and zeolite were shown to reduce the impact of bacterial communities on GHGs emissions. In summary, this study revealed that biochar and zeolite can effectively reduce GHG emissions during composting by altering the compost microenvironment and regulating microbial community structure. Such findings are valuable for facilitating high-quality resource recovery of organic solid waste.

Metabolism of toxic benzonitrile and hydroxybenzonitrile isomers via several distinct central pathway intermediates in a catabolically robust Burkholderia sp.

Aromatic nitriles are of considerable environmental concern, because of their hazardous impacts on the health of both humans and wildlife. In the present study, Burkholderia sp. strain BC1 was observed to be capable of utilizing toxic benzonitrile and hydroxybenzonitrile isomers singly, as sole carbon and energy sources. The results of chromatographic and spectrometric analyses in combination with oxygen uptake and enzyme activity studies, revealed the metabolism of benzonitrile as well as 2-, 3-, and 4-hydroxybenzonitriles by nitrile hydratase-amidase to the corresponding carboxylates. These carboxylates were further metabolized via central pathways, namely benzoate-catechol, salicylate-catechol, 3-hydroxybenzoate-gentisate and 4-hydroxybenzoate-protocatechute pathways in strain BC1, ultimately leading to the TCA cycle intermediates. Studies also evaluated substrate specificity profiles of both nitrile hydratase and amidase(s) involved in the denitrification of the nitriles. In addition, a few metabolic crosstalk events due to the induction of multiple operons by central metabolites were appraised in strain BC1. The present study illustrates the broad degradative potential of strain BC1, harboring diverse catabolic machinery of biotechnological importance, elucidating pathways for the assimilation of benzonitrile and that of hydroxybenzonitrile isomers for the first time.