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Cancer Cell Feb 2022Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but...
Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but how the metabolites impact CRC is largely unknown. We interrogated fecal metabolites associated with mouse models of colon tumorigenesis with varying mutational load. We find that microbial metabolites from healthy mice or humans are growth-repressive, and this response is attenuated in mice and patients with CRC. Microbial profiling reveals that Lactobacillus reuteri and its metabolite, reuterin, are downregulated in mouse and human CRC. Reuterin alters redox balance, and reduces proliferation and survival in colon cancer cells. Reuterin induces selective protein oxidation and inhibits ribosomal biogenesis and protein translation. Exogenous Lactobacillus reuteri restricts colon tumor growth, increases tumor reactive oxygen species, and decreases protein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.
Topics: Animals; Biomarkers; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Disease Models, Animal; Energy Metabolism; Gastrointestinal Microbiome; Glutathione; Glyceraldehyde; Host Microbial Interactions; Humans; Intestinal Mucosa; Metabolomics; Metagenomics; Mice; Models, Biological; Oxidation-Reduction; Oxidative Stress; Propane; Signal Transduction; Xenograft Model Antitumor Assays
PubMed: 34951957
DOI: 10.1016/j.ccell.2021.12.001 -
Cell Metabolism Jan 2020Iron is a central micronutrient needed by all living organisms. Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial...
Iron is a central micronutrient needed by all living organisms. Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial populations and for host health. How symbiotic relationships between hosts and native microbes persist during times of iron limitation is unclear. Here, we demonstrate that indigenous bacteria possess an iron-dependent mechanism that inhibits host iron transport and storage. Using a high-throughput screen of microbial metabolites, we found that gut microbiota produce metabolites that suppress hypoxia-inducible factor 2α (HIF-2α) a master transcription factor of intestinal iron absorption and increase the iron-storage protein ferritin, resulting in decreased intestinal iron absorption by the host. We identified 1,3-diaminopropane (DAP) and reuterin as inhibitors of HIF-2α via inhibition of heterodimerization. DAP and reuterin effectively ameliorated systemic iron overload. This work provides evidence of intestine-microbiota metabolic crosstalk that is essential for systemic iron homeostasis.
Topics: Adolescent; Animals; Anti-Bacterial Agents; Basic Helix-Loop-Helix Transcription Factors; Cell Line; Cell Proliferation; Diamines; Dimerization; Duodenum; Feces; Female; Ferritins; Gastrointestinal Microbiome; Glyceraldehyde; Homeostasis; Humans; Iron; Lactobacillus; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Organoids; Probiotics; Propane; Signal Transduction
PubMed: 31708445
DOI: 10.1016/j.cmet.2019.10.005 -
Microbial Cell Factories Nov 2020The development of sustainable routes to the bio-manufacture of gaseous hydrocarbons will contribute widely to future energy needs. Their realisation would contribute... (Review)
Review
The development of sustainable routes to the bio-manufacture of gaseous hydrocarbons will contribute widely to future energy needs. Their realisation would contribute towards minimising over-reliance on fossil fuels, improving air quality, reducing carbon footprints and enhancing overall energy security. Alkane gases (propane, butane and isobutane) are efficient and clean-burning fuels. They are established globally within the transportation industry and are used for domestic heating and cooking, non-greenhouse gas refrigerants and as aerosol propellants. As no natural biosynthetic routes to short chain alkanes have been discovered, de novo pathways have been engineered. These pathways incorporate one of two enzymes, either aldehyde deformylating oxygenase or fatty acid photodecarboxylase, to catalyse the final step that leads to gas formation. These new pathways are derived from established routes of fatty acid biosynthesis, reverse β-oxidation for butanol production, valine biosynthesis and amino acid degradation. Single-step production of alkane gases in vivo is also possible, where one recombinant biocatalyst can catalyse gas formation from exogenously supplied short-chain fatty acid precursors. This review explores current progress in bio-alkane gas production, and highlights the potential for implementation of scalable and sustainable commercial bioproduction hubs.
Topics: Alkanes; Biofuels; Biosynthetic Pathways; Butanes; Carboxy-Lyases; Fatty Acids; Gases; Genetic Engineering; Industrial Microbiology; Metabolic Engineering; Oxidation-Reduction; Oxygenases; Propane; Synthetic Biology
PubMed: 33187524
DOI: 10.1186/s12934-020-01470-6 -
Environmental Science & Technology Jul 2023Exposure pathways to the carcinogen benzene are well-established from tobacco smoke, oil and gas development, refining, gasoline pumping, and gasoline and diesel...
Exposure pathways to the carcinogen benzene are well-established from tobacco smoke, oil and gas development, refining, gasoline pumping, and gasoline and diesel combustion. Combustion has also been linked to the formation of nitrogen dioxide, carbon monoxide, and formaldehyde indoors from gas stoves. To our knowledge, however, no research has quantified the formation of benzene indoors from gas combustion by stoves. Across 87 homes in California and Colorado, natural gas and propane combustion emitted detectable and repeatable levels of benzene that in some homes raised indoor benzene concentrations above well-established health benchmarks. Mean benzene emissions from gas and propane burners on high and ovens set to 350 °F ranged from 2.8 to 6.5 μg min, 10 to 25 times higher than emissions from electric coil and radiant alternatives; neither induction stoves nor the food being cooked emitted detectable benzene. Benzene produced by gas and propane stoves also migrated throughout homes, in some cases elevating bedroom benzene concentrations above chronic health benchmarks for hours after the stove was turned off. Combustion of gas and propane from stoves may be a substantial benzene exposure pathway and can reduce indoor air quality.
Topics: Air Pollution, Indoor; Benzene; Propane; Gasoline; Household Products; Cooking; Air Pollutants
PubMed: 37319002
DOI: 10.1021/acs.est.2c09289 -
ACS Omega Feb 2022To expand the knowledge on hydrocarbon selective catalytic reduction (SCR) and follow the research steps of methane-SCR and propane-SCR in our previous work, we studied...
To expand the knowledge on hydrocarbon selective catalytic reduction (SCR) and follow the research steps of methane-SCR and propane-SCR in our previous work, we studied the characteristics of propane adsorption on In/BEA zeolite, explored the NO and NO activation process on a propane adsorbed catalyst, and calculated the reaction enthalpy of two reaction pathways. Results showed that O site in the L-model (the [InO]/BEA structure) was the main active site in the adsorption process, and any of the carbon atoms in the propane molecule could react with it, with a lower adsorption energy than methane (-3.20 vs -2.98 eV). Also, NO or NO could not be directly activated on the propane adsorbed catalyst, indicating that the process may be complicated. In addition, propane reduces the NO or NO molecule with two different pathways and the final products were less stable than those of methane (-5.6 vs -20 eV). These results could explain the fact that propane and methane had different reaction temperatures and would further deepen our understanding of the propane-SCR process.
PubMed: 35155942
DOI: 10.1021/acsomega.1c06414 -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Insecticides; Mutagenicity Tests; Mutagens; Neoplasms; Neoplasms, Experimental; Propane
PubMed: 10476458
DOI: No ID Found -
The ISME Journal Jul 2022Natural gas seeps release significant amounts of methane and other gases including ethane and propane contributing to global climate change. In this study, bacterial...
Natural gas seeps release significant amounts of methane and other gases including ethane and propane contributing to global climate change. In this study, bacterial actively consuming short-chain alkanes were identified by cultivation, whole-genome sequencing, and stable-isotope probing (SIP)-metagenomics using C-propane and C-ethane from two different natural gas seeps, Pipe Creek and Andreiasu Everlasting Fire. Nearly 100 metagenome-assembled genomes (MAGs) (completeness 70-99%) were recovered from both sites. Among these, 16 MAGs had genes encoding the soluble di-iron monooxygenase (SDIMO). The MAGs were affiliated to Actinobacteria (two MAGs), Alphaproteobacteria (ten MAGs), and Gammaproteobacteria (four MAGs). Additionally, three gaseous-alkane degraders were isolated in pure culture, all of which could grow on ethane, propane, and butane and possessed SDIMO-related genes. Two Rhodoblastus strains (PC2 and PC3) were from Pipe Creek and a Mycolicibacterium strain (ANDR5) from Andreiasu. Strains PC2 and PC3 encoded putative butane monooxygenases (MOs) and strain ANDR5 contained a propane MO. Mycolicibacterium strain ANDR5 and MAG19a, highly abundant in incubations with C-ethane, share an amino acid identity (AAI) of 99.3%. We show using a combination of enrichment and isolation, and cultivation-independent techniques, that these natural gas seeps contain a diverse community of active bacteria oxidising gaseous-alkanes, which play an important role in biogeochemical cycling of natural gas.
Topics: Alkanes; Bacteria; Butanes; Ethane; Gases; Mixed Function Oxygenases; Natural Gas; Phylogeny; Propane
PubMed: 35319019
DOI: 10.1038/s41396-022-01211-0 -
Nature Genetics Nov 2020Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from...
Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from mice chronically exposed to 1 of 20 known or suspected human carcinogens, we reveal that most agents do not generate distinct mutational signatures or increase mutation burden, with most mutations, including driver mutations, resulting from tissue-specific endogenous processes. We identify signatures resulting from exposure to cobalt and vinylidene chloride and link distinct human signatures (SBS19 and SBS42) with 1,2,3-trichloropropane, a haloalkane and pollutant of drinking water, and find these and other signatures in human tumor genomes. We define the cross-species genomic landscape of tumors induced by an important compendium of agents with relevance to human health.
Topics: Animals; Carcinogenesis; Carcinogens; DNA Mutational Analysis; Environmental Pollutants; Female; Genome; Humans; Male; Mice; Mutation; Mutation Rate; Propane; Species Specificity
PubMed: 32989322
DOI: 10.1038/s41588-020-0692-4 -
Applied and Environmental Microbiology Jun 2021The families of copper-containing membrane-bound monooxygenases (CuMMOs) and soluble di-iron monooxygenases (SDIMOs) are involved not only in methane oxidation but also...
Horizontal Gene Transfer of Genes Encoding Copper-Containing Membrane-Bound Monooxygenase (CuMMO) and Soluble Di-iron Monooxygenase (SDIMO) in Ethane- and Propane-Oxidizing Bacteria.
The families of copper-containing membrane-bound monooxygenases (CuMMOs) and soluble di-iron monooxygenases (SDIMOs) are involved not only in methane oxidation but also in short-chain alkane oxidation. Here, we describe sp. strain ZPP, a bacterium able to grow with ethane or propane as the sole carbon and energy source, and report on the horizontal gene transfer (HGT) of actinobacterial hydrocarbon monooxygenases (HMOs) of the CuMMO family and the sMMO (soluble methane monooxygenase)-like SDIMO in the genus . The key function of HMO in strain ZPP for propane oxidation was verified by allylthiourea inhibition. The HMO genes (designated ) and those encoding sMMO-like SDIMO (designated ) are located on a linear megaplasmid (pRZP1) of strain ZPP. Comparative genomic analysis of similar plasmids indicated the mobility of these plasmids within the genus . The plasmid pRZP1 in strain ZPP could be conjugatively transferred to a recipient Rhodococcus erythropolis strain in a mating experiment and showed similar ethane- and propane-consuming activities. Finally, our findings demonstrate that the horizontal transfer of plasmid-based CuMMO and SDIMO genes confers the ability to use ethane and propane on the recipient. CuMMOs and SDIMOs initiate the aerobic oxidation of alkanes in bacteria. Here, the supposition that horizontally transferred plasmid-based CuMMO and SDIMO genes confer on the recipient similar abilities to use ethane and propane was proposed and confirmed in This study is a living example of HGT of CuMMOs and SDIMOs and outlines the plasmid-borne properties responsible for gaseous alkane degradation. Our results indicate that plasmids can support the rapid evolution of enzyme-mediated biogeochemical processes.
Topics: Bacterial Proteins; Ethane; Gene Transfer, Horizontal; Genes, Bacterial; Mixed Function Oxygenases; Oxidation-Reduction; Plasmids; Propane; Rhodococcus
PubMed: 33962978
DOI: 10.1128/AEM.00227-21 -
The Journal of Physical Chemistry. C,... May 2019We report a systematic study of relaxation dynamics of hyperpolarized (HP) propane and HP propane-d prepared by heterogeneous pairwise parahydrogen addition to propylene...
We report a systematic study of relaxation dynamics of hyperpolarized (HP) propane and HP propane-d prepared by heterogeneous pairwise parahydrogen addition to propylene and propylene-d respectively. Long-lived spin states (LLS) created for these molecules at the low magnetic field of 0.0475 T were employed for this study. The parahydrogen-induced overpopulation of a HP propane LLS decays exponentially with time constant (T) approximately 3-fold greater than the corresponding T values. Both T and T increase linearly with propane pressure in the range from 1 atm (the most biomedically relevant conditions for pulmonary MRI) to 5 atm. The T value of HP propane gas at 1 atm is ~3 s. Deuteration of the substrate (propylene-d) yields hyperpolarized propane-d gas with T values approximately 20% shorter than those of hyperpolarized fully protonated propane gas, indicating that deuteration does not benefit the lifetime of the LLS HP state. The use of pH or Xe/N buffering gas during heterogeneous hydrogenation reaction (leading to production of 100% HP propane (no buffering gas) versus 43% HP propane gas (with 57% buffering gas) composition mixtures) results in (i) no significant changes in T, (ii) decrease of T values (by 35±7% and 8±7% respectively); and (iii) an increase of the polarization levels of HP propane gas with a propane concentration decrease (by 1.6±0.1-fold and 1.4±0.1-fold respectively despite the decrease in T, which leads to disproportionately greater polarization losses during HP gas transport). Moreover, we demonstrate the feasibility of HP propane cryo-collection (which can be potentially useful for preparing larger amounts of concentrated HP propane, when buffering gas is employed), and T of liquefied HP propane reaches 14.7 seconds, which is greater than the T value of HP propane gas at any pressure studied. Finally, we have explored the utility of using a partial Spin-Lock Induced Crossing (SLIC) radio frequency (RF) pulse sequence for converting the overpopulated LLS into observable H nuclear magnetization at low magnetic field. We find that (i) the bulk of the overpopulated LLS is retained even when the optimal or near-optimal values of SLIC pulse duration are employed, and (ii) the overpopulated LLS of propane is also relatively immune to strong RF pulses-thereby, indicating that LLS is highly suitable as a spin-polarization reservoir in the context of NMR/MRI detection applications. The presented findings may be useful for improving the levels of polarization of HP propane produced by HET-PHIP via the use of an inert buffer gas; increasing the lifetime of the HP state during preparation and storage; and developing efficient approaches for ultrafast MR imaging of HP propane in the context of biomedical applications of HP propane gas, including its potential use as an inhalable contrast agent.
PubMed: 31798763
DOI: 10.1021/acs.jpcc.9b01538