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Biotechnology For Biofuels 2018As a versatile platform chemical, construction of microbial catalysts for free octanoic acid production from biorenewable feedstocks is a promising alternative to...
BACKGROUND
As a versatile platform chemical, construction of microbial catalysts for free octanoic acid production from biorenewable feedstocks is a promising alternative to existing petroleum-based methods. However, the bio-production strategy has been restricted by the low capacity of inherent fatty acid biosynthesis. In this study, a combination of integrated computational and experimental approach was performed to manipulate the existing metabolic network, with the objective of improving bio-octanoic acid production.
RESULTS
First, a customized OptForce methodology was run to predict a set of four genetic interventions required for production of octanoic acid at 90% of the theoretical yield. Subsequently, all the ten candidate proteins associated with the predicted interventions were regulated individually, as well as in contrast to the combination of interventions as suggested by the OptForce strategy. Among these enzymes, increased production of 3-hydroxy-acyl-ACP dehydratase (FabZ) resulted in the highest increase (+ 45%) in octanoic acid titer. But importantly, the combinatorial application of FabZ with the other interventions as suggested by OptForce further improved octanoic acid production, resulting in a high octanoic acid-producing strain + Δ Δ Δ (TE10) (+ 61%). Optimization of expression, medium pH, and C:N ratio resulted in the identified strain producing 500 mg/L of C8 and 805 mg/L of total FAs, an 82 and 155% increase relative to wild-type MG1655 (TE10) in shake flasks. The best engineered strain produced with high selectivity (> 70%) and extracellularly (> 90%) up to 1 g/L free octanoic acid in minimal medium fed-batch culture.
CONCLUSIONS
This work demonstrates the effectiveness of integration of computational strain design and experimental characterization as a starting point in rewiring metabolism for octanoic acid production. This result in conjunction with the results of other studies using OptForce in strain design demonstrates that this strategy may be also applicable to engineering for other customized bioproducts.
PubMed: 29619083
DOI: 10.1186/s13068-018-1078-z -
ACS Synthetic Biology May 2021Octanoic acid is an industrially relevant compound with applications in antimicrobials or as a precursor for biofuels. Microbial biosynthesis through yeast is a...
Octanoic acid is an industrially relevant compound with applications in antimicrobials or as a precursor for biofuels. Microbial biosynthesis through yeast is a promising alternative to current unsustainable production methods. To increase octanoic acid titers in , we use a previously developed biosensor that is based on the octanoic acid responsive promotor coupled to GFP. We establish a biosensor strain amenable for high-throughput screening of an octanoic acid producer strain library. Through development, optimization, and execution of a high-throughput screening approach, we were able to detect two new genetic targets, and , which increased octanoic acid titers through combined overexpression by about 55% compared to the parental strain. Neither target has yet been reported to be involved in fatty acid biosynthesis. The presented methodology can be employed to screen any genetic library and thereby more genes involved in improving octanoic acid production can be detected in the future.
Topics: Biosensing Techniques; Caprylates; Fatty Acids; Flow Cytometry; Gene Expression; Gene Library; Green Fluorescent Proteins; High-Throughput Screening Assays; Metabolic Engineering; Microorganisms, Genetically-Modified; Phosphotransferases (Phosphate Group Acceptor); Promoter Regions, Genetic; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Serine Proteases
PubMed: 33979526
DOI: 10.1021/acssynbio.0c00600 -
Current Protein & Peptide Science 2020Medium-chain fatty acids (MCFAs) are the main form of Medium Chain Triglycerides (MCTs) utilized by monogastric animals. MCFAs can be directly absorbed and supply rapid... (Review)
Review
Medium-chain fatty acids (MCFAs) are the main form of Medium Chain Triglycerides (MCTs) utilized by monogastric animals. MCFAs can be directly absorbed and supply rapid energy to promote the renewal and repair of intestinal epithelial cells, maintain the integrity of intestinal mucosal barrier function, and reduce inflammation and stress. In our review, we pay more attention to the role of MCFAs on intestinal microbiota and mucosa immunity to explore MCFA's positive effect. It was found that MCFAs and their esterified forms can decrease pathogens while increasing probiotics. In addition, being recognized via specific receptors, MCFAs are capable of alleviating inflammation to a certain extent by regulating inflammation and immune-related pathways. MCFAs may also have a certain value to relieve intestinal allergy and inflammatory bowel disease (IBD). Unknown mechanism of various MCFA characteristics still causes dilemmas in the application, thus MCFAs are used generally in limited dosages and combined with short-chain organic acids (SOAs) to attain ideal results. We hope that further studies will provide guidance for the practical use of MCFAs in animal feed.
Topics: Animal Feed; Animals; Caprylates; Colitis, Ulcerative; Crohn Disease; Cytokines; Decanoic Acids; Gene Expression Regulation; Humans; Immunity, Mucosal; Intestinal Absorption; Intestines; Irritable Bowel Syndrome; Lauric Acids; NF-kappa B; Stomach; Triglycerides
PubMed: 31889482
DOI: 10.2174/1389203721666191231145901 -
The Journal of Physical Chemistry. C,... Feb 2024Perfluorooctanoic acid (PFOA) is an environmentally prevalent and persistent organic pollutant with toxic and bioaccumulative properties. Despite the known importance of...
Perfluorooctanoic acid (PFOA) is an environmentally prevalent and persistent organic pollutant with toxic and bioaccumulative properties. Despite the known importance of perfluorinated pollutants in the global environment, molecular-level details of the physicochemical behavior of PFOA on aqueous interfaces remain poorly understood. Here, we utilized two surface-specific techniques, vibrational sum frequency generation spectroscopy (SFG) and surface tensiometry, to investigate the pH-induced structural changes of PFOA and octanoic acid (OA) and determined the apparent p at the air-water surface. The SFG spectra and surface activity model were investigated over a wide range of pHs. With the surface tension measurements, the surface p values for OA and PFOA are determined to be 3.8 ± 0.1 and 2.2 ± 0.2, respectively. These results could provide insights into improved remediation of PFOAs and may impact climate modeling of perfluorinated alkyl chain molecules.
PubMed: 38352857
DOI: 10.1021/acs.jpcc.3c07235 -
Methods in Molecular Biology (Clifton,... 2021The liver is at the crossroad of key metabolic processes, which include detoxification, glycolipidic storage and export, and protein synthesis. The gut-liver axis,...
The liver is at the crossroad of key metabolic processes, which include detoxification, glycolipidic storage and export, and protein synthesis. The gut-liver axis, moreover, provides hepatocytes with a series of bacterial products and metabolites, which contribute to maintain liver function in health and disease. Breath tests (BTs) are developed as diagnostic tools for indirect, rapid, noninvasive assessment of several metabolic processes in the liver. BTs monitor the appearance of CO in breath as a marker of a specific substrate metabolized in the liver, typically within microsomes, cytosol, or mitochondria. The noninvasiveness of BTs originates from the use of the, nonradioactive, naturally occurring stable isotope C marking a specific substrate which is metabolized in the liver, leading to the appearance of CO in expired air. Some substrates (ketoisocaproic acid, methionine, and octanoic acid) provide information about dynamic liver mitochondrial function in health and disease. In humans, the application of C-breath tests ranges from nonalcoholic and alcoholic liver diseases to liver cirrhosis, hepatocarcinoma, preoperative and postoperative assessment of liver function, and drug-induced liver damage. C-BTs are an indirect, cost-effective, and easy method to evaluate dynamic liver function and gastric kinetics in health and disease, with ongoing studies focusing on further applications in clinical medicine.
Topics: Biomarkers; Breath Tests; Carbon Dioxide; Carbon Isotopes; Humans; Liver Diseases; Liver Function Tests; Mitochondria, Liver; Predictive Value of Tests
PubMed: 34096004
DOI: 10.1007/978-1-0716-1433-4_11 -
Journal of Medicinal Food Nov 2017Capric acid and caprylic acid are the dietary food components. They are found to inhibit the virulence factors like morphogenesis, adhesion, and biofilm formation in the...
Capric acid and caprylic acid are the dietary food components. They are found to inhibit the virulence factors like morphogenesis, adhesion, and biofilm formation in the human pathogenic yeast Candida albicans. Our study demonstrated that yeast-to-hyphal signal transduction pathways were affected by capric acid and caprylic acid. The expression profile of genes associated with serum-induced morphogenesis showed reduced expressions of Cdc35, Hwp1, Hst7, and Cph1 by the treatment with both the fatty acids. Cell elongation gene, Ece1, was surprisingly downregulated by 5208-fold by the treatment of caprylic acid. Nrg1 and Tup1, negative regulators of hyphal formation, were overexpressed in presence of capric or caprylic acid. Cell cycle studies revealed that capric and caprylic acids arrested cell cycle at G2/M and S phase. Targeting the virulence factors like yeast-to-hyphal transition is efficacious for treatment of opportunistic fungal infections. This research suggests that both capric and caprylic acid may be effective interventions for treating C. albicans yeast infections.
Topics: Antifungal Agents; Candida albicans; Caprylates; Cell Cycle; Decanoic Acids; Fungal Proteins; Gene Expression Regulation, Fungal; Hyphae; Signal Transduction; Virulence Factors
PubMed: 28922057
DOI: 10.1089/jmf.2017.3971 -
Molecular Biology Reports Jun 2021Dysfunction of the gastrointestinal tract (GIT) is one of the most common non-motor symptom of Parkinson's Disease (PD). Pathological processes causing PD were suggested...
BACKGROUND
Dysfunction of the gastrointestinal tract (GIT) is one of the most common non-motor symptom of Parkinson's Disease (PD). Pathological processes causing PD were suggested to initiate in the enteric nervous system (ENS) and proceed to the central nervous system (CNS). There are studies showing that low-carbohydrate ketogenic diets can improve motor symptoms of PD. Caprylic acid (C8) is the principal fatty acid component of the medium-chain triglycerides in the ketogenic diets. In this study, we aimed to evaluate the effects of caprylic acid, in neurotoxin exposed zebrafish focusing on the relationship between intestinal and brain oxidative stress and inflammation.
METHODS
Adult zebrafish were exposed to rotenone (5 μg/L) (R group) and caprylic acid (20 and 60 mg/mL) (L + HDCA and R + HDCA groups) for 30 days. At the end of 30 days locomotor activities were determined. Levels of lipid peroxidation (LPO), nitric oxide, glutathione and superoxide dismutase and glutathione S-transferase activities were determined by spectrophotometric methods and gene expressions of tnf⍺, il1, il6, il21, ifnɣ and bdnf were evaluated by RT-PCR in the brain and intestinal tissues of zebrafish.
RESULTS
Caprylic acid ameliorated LPO, NO, SOD and the expressions of tnf⍺, il1, il6, il21, ifnɣ and bdnf in brain and intestines. Locomotor activities were only ameliorated in high dose R + HDCA group.
CONCLUSIONS
Caprylic acid ameliorated the neurotoxin-induced oxidative stress and inflammation both in the brain and intestines and enhanced locomotor activity in zebrafish.
Topics: Animals; Brain; Brain-Gut Axis; Caprylates; Disease Models, Animal; Gastrointestinal Tract; Glutathione; Inflammation; Lipid Peroxidation; Oxidative Stress; Parkinson Disease; Rotenone; Superoxide Dismutase; Zebrafish; Zebrafish Proteins
PubMed: 34228274
DOI: 10.1007/s11033-021-06532-5 -
Journal of Chromatography. A Sep 2023Poly(ethyleneimine) (PEI) modified silica spheres were used to graft butyric acid and octanoic acid onto their surfaces, forming two stationary phases named Sil-PEI-BAD... (Comparative Study)
Comparative Study
Poly(ethyleneimine) (PEI) modified silica spheres were used to graft butyric acid and octanoic acid onto their surfaces, forming two stationary phases named Sil-PEI-BAD and Sil-PEI-CAD, respectively. Characterized methods including fourier transform infrared spectroscopy (FT-IR), elemental analysis (EA) and thermogravimetric analysis (TGA) were utilized to determine the successful synthesis of these two stationary phase materials. The chromatographic performance of these two stationary phases was analyzed with hydrophobic and hydrophilic compounds as analytes. Compared with Sil-PEI-CAD column, Sil-PEI-BAD column was more effective in separating hydrophilic compounds including nucleosides, alkaloids and vitamins. Hydrophobic substances including polycyclic aromatic hydrocarbons (PAHs) and alkylbenzenes obtained excellent separation results on Sil-PEI-CAD column than Sil-PEI-BAD column. Additionally, according to the separation of phenols, Sil-PEI-CAD column can be used in HILIC/RPLC mixed-mode. The results showed that the properties and retention mechanisms of the prepared stationary phases depended on the length of the alkyl chains bonded on the silica surface.
Topics: Chromatography, Reverse-Phase; Hydrophobic and Hydrophilic Interactions; Nucleosides; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared
PubMed: 37544237
DOI: 10.1016/j.chroma.2023.464268 -
The Laryngoscope Aug 2019The purpose of this study was to determine the effects of octanoic acid on acoustic, perceptual, and functional aspects of essential voice tremor (EVT). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES/HYPOTHESIS
The purpose of this study was to determine the effects of octanoic acid on acoustic, perceptual, and functional aspects of essential voice tremor (EVT).
STUDY DESIGN
Prospective, double-blind, placebo-controlled, crossover study.
METHODS
Sixteen participants with a diagnosis of EVT were randomized to a 3-week dosing condition of octanoic acid or placebo, followed by a 2-week washout period and crossover to the other condition for an additional 3 weeks. Baseline and post-testing sessions were completed before and at the completion of each condition. Primary outcome measures were the magnitude of amplitude and frequency tremor, measured from the acoustic signal. Secondary outcomes were auditory-perceptual ratings of tremor severity and self-ratings of voice handicap.
RESULTS
Magnitude of amplitude and frequency tremor were significantly lower after 3 weeks of octanoic acid dosing as compared to the placebo condition. Auditory-perceptual ratings of tremor severity did not show significant differences between conditions. A trend toward better voice was seen for the sustained vowel ratings, but not the sentence-level ratings. No significant differences between conditions were seen on self-reported voice disability as assessed on the Voice Handicap Index-10.
CONCLUSIONS
The results of this controlled investigation support the potential utility of octanoic acid for reducing the magnitude of tremor in people with EVT. Further research is needed to determine whether different dosing or treatment combinations can improve functional communication in EVT.
LEVEL OF EVIDENCE
1 Laryngoscope, 129:1882-1890, 2019.
Topics: Aged; Caprylates; Cross-Over Studies; Double-Blind Method; Essential Tremor; Female; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Treatment Outcome; Voice; Voice Disorders
PubMed: 30585335
DOI: 10.1002/lary.27695 -
Journal of Assisted Reproduction and... Oct 2015The purpose of this study was to determine the effect of the protein stabilizer octanoic acid on blastocyst development, implantation, and fetal growth in a murine model.
PURPOSE
The purpose of this study was to determine the effect of the protein stabilizer octanoic acid on blastocyst development, implantation, and fetal growth in a murine model.
METHODS
One-cell mouse embryos were collected and individually cultured in medium supplemented with recombinant human serum albumin for 96 h at 5 % oxygen in an EmbryoScope. Embryos were randomly allocated to four octanoic acid groups (0, 400, 800, or 1200 μM). Blastocyst development and cell cycle timings were calculated at 96 h of culture, and experiments were repeated in triplicate. Blastocysts were stained and fixed at 96 h for differential cell counts. Following 96 h of culture, blastocysts were transferred to recipients to determine implantation rates and fetal and placental weights.
RESULTS
Blastocyst development, hatching rates, developmental kinetics, and total number of cells were negatively affected by octanoic acid at concentrations commonly used in human IVF. Implantation was not affected by octanoic acid but fetal and placental weights at 800 μM octanoic acid were increased relative to control.
CONCLUSIONS
Octanoic acid, a standard additive to human protein supplements used in IVF, can have long-term negative effects on embryonic and fetal development. The use of octanoic acid for human embryo culture should be monitored and reduced.
Topics: Animals; Blastocyst; Caprylates; Culture Media; Embryo Culture Techniques; Embryo Implantation; Embryo Transfer; Embryonic Development; Female; Humans; Male; Mice, Inbred Strains; Placenta; Pregnancy; Serum Albumin
PubMed: 26342329
DOI: 10.1007/s10815-015-0560-9