Preparation and Evaluation of Poly-γ-Glutamic Acid Hydrogel Mixtures with Basic Drugs or Acidic Drugs: Effect on Ease of Swallowing and Taste Masking

The purpose of this study was to prepare a poly-γ-glutamic acid hydrogel (PGA gel), to examine its ease of swallowing using texture profile analysis (TPA) and to evaluate its taste-masking effects on basic or acidic drugs using the artificial taste sensor. Using TPA, 0.5% and 1.0% PGA gels, 0.5% and 1.0% agar and 1.0% ι-carrageenan in the absence of drug was examined the hardness, adhesiveness and cohesiveness, ranked according to permission criteria published by the Japanese Consumers Affairs Agency. 0.5% PGA gel and 1.0% agar were classified into grade II. In the taste sensor measurement, the bitterness suppressions by 0.5% PGA gel were larger than that by 1.0% agar in all drugs and the bitterness suppressions of basic drugs in 0.5% PGA gel were more potent than those of acidic drugs in 0.5% PGA gel. 1H-nuclear magnetic resonance spectroscopic analysis was carried out to examine the difference in mechanism of bitterness suppression between basic drugs and acidic drugs mixed with PGA gel. The signals of the proton nearest to the nitrogen atom of basic drugs shifted clearly upfield, suggesting an interaction between the amino group of basic drugs and the carboxyl group of PGA gel. In conclusion, PGA gel is expected to be a useful excipient in formulations contained various drugs, especially basic drugs;it also has advantage for not only increasing ease of swallowing but also masking the bitterness of drugs even though a small amount of a single drug dose might be preferred.

An Anionic Polymer Incorporating Low Amounts of Hydrophobic Residues Is a Multifunctional Surfactant. Part 2: Emulsification, Moisture Absorption, and Moisture Retention of Alkyl Esterified Poly-γ-Glutamic Acid

In the accompanying paper (Part 1), we showed that the fatty acid moiety and the acidity of the polysaccharide-backbone of a fatty acid-containing polysaccharide might be involved in its emul-sification, moisture absorption, and moisture retention abilities. In this study, we synthesized alkyl esterified poly-γ-glutamic acid (PGA) with various chain lengths and degrees of substitution of the alkyl moieties to examine how hydrophobic groups incorporated in the anionic polymer contribute to enhanced emulsification, moisture absorption, and moisture retention. With a low degree of alkylation of PGA, these abilities were drastically improved. To improve the moisture absorption of PGA, alkylation with a short chain length is effective in forming interspaces between PGA chains to trap water molecules. Hydrophobic-hydrophilic balance may also be important to improve the emulsification and moisture retention abilities of PGA alkylates. To the best of our knowledge, this is the first report of the relationship between the structure and the multifunctional abilities of an anionic polymer incorporated with a small amount of hydrophobic residue. PGA alkylates, as well as fatty acid-containing polysaccharides, have potential use as multifunctional surfactants throughout various industries.

Adsorption of La^(3+) and Ce^(3+) by poly-γ-glutamic acid crosslinked with polyvinyl alcohol

With the exploitation of rare earth ore, more and more rare earth elements came into groundwater, caused waste of resources and toxicity to the organisms. This study aimed to find an efficient adsorption material to mitigate the above issue. Through doping polyvinyl alcohol with poly-γ-glutamic acid, an immobilised PSP gel particle was produced and had the adsorption rate of La3＋ up to 97.10%. The factors including initial concentration of La3＋ or Ce3＋, adsorbent dosage, pH and temperature of the solution, which potentially affected the adsorption rate and were studied in batch mode. It was found that the optimum adsorption conditions were composed of 50 mg/L La3 VCe3＋ of initial concentration, 600 mg/L （dry mass） biomass for adsorption, pH 6, temperature 30 ℃, 150 r/min rotational speed, and 1 h adsorption time. The selective adsorption of 15 different rare earth ions in mixed aqueous solu- tions were investigated. However, no significant selective differences were observed. Scanning electron microscopy showed that the morphological characteristic of the novel gel was its porous structure, while polyvinyl alcohol gel had a compact structure. Fourier transform infrared spectroscopy suggested that carboxyl groups in the poly-γ-glutamic acid might played a key role in the adsorption process. The adsorption mechanism forecasted to be cation exchange between -COOH and R3＋. The adsorption kinetic and thermodynamic process for La3＋ and Ce3＋ was consistent with the pseudo-second-order equation and Langmuir adsorption isotherm model. It demonstrated that PSP gels particles were useful for removing REEs from wastewater.

Enhanced production of poly-γ-glutamic acid via optimizing the expression cassette of Vitreoscilla hemoglobin in Bacillus licheniformis

Poly-γ-glutamic acid(γ-PGA)is a natural polymer with various applications,and its high-viscosity hinders ox-ygen transmission and improvement of synthesis level.Vitreoscilla hemoglobin(VHB)has been introduced into various hosts as oxygen carrier,however,its expression strength and contact efficiency with oxygen hindered efficient oxygen transfer and metabolite synthesis.Here,we want to optimize the expression cassette of VHB for γ-PGA production.Firstly,our results implied that γ-PGA yields were enhanced when introducing twin-arginine translocation(Tat)signal peptides(SP_(YwbN),SP_(PhoD) and SP_(TorA))into VHB expression cassette,and the best per-formance was attained by SP YwbN from Bacillus subtilis,theγ-PGA yield of which was 18.53% higher than that of control strain,and intracellular ATP content and oxygen transfer coefficient(K_(L)a)were increased by 29.71% and 73.12%,respectively,indicating that VHB mediated by SP YwbN benefited oxygen transfer and ATP generation forγ-PGA synthesis.Furthermore,four promoters were screened,and P vgb was proven as the more suitable promoter for VHB expression andγ-PGA synthesis,andγ-PGA yield of attaining strain WX/pPvgb-YwbN-Vgb was further increased to 40.59 g/L by 10.18%.Finally,WX/pPvgb-YwbN-Vgb was cultivated in 3 L fermentor for fed-batch fermentation,and 46.39 g/Lγ-PGA was attained by glucose feeding,increased by 49.26%compared with the initial yield(31.01 g/L).Taken together,this study has attained an efficient VHB expression cassette for oxygen transfer andγ-PGA synthesis,which could also be applied in the production of other metabolites.

Genomic and metabolomic analysis of Bacillus licheniformis with enhanced poly-γ-glutamic acid production through atmospheric and room temperature plasma mutagenesis

Poly-γ-glutamic acid is an extracellular polymeric substance with various applications owing to its valuable properties of biodegradability,flocculating activity,water solubility,and nontoxicity.However,the ability of natural strains to produce poly-γ-glutamic acid is low.Atmospheric and room temperature plasma was applied in this study to conduct mutation breeding of Bacillus licheniformis CGMCC 2876,and a mutant strain M32 with an 11%increase in poly-γ-glutamic acid was obtained.Genome resequencing analysis identified 7 nonsynonymous mutations of ppsC encoding lipopeptide synthetase associated with poly-γ-glutamic acid metabolic pathways.From molecular docking,more binding sites and higher binding energy were speculated between the mutated plipastatin synthase subunit C and glutamate,which might contribute to the higher poly-γ-glutamic acid production.Moreover,the metabolic mechanism analysis revealed that the upregulated amino acids of M32 provided substrates for glutamate and promoted the conversion between L-and D-glutamate acids.In addition,the glycolytic pathway is enhanced,leading to a better capacity for using glucose.The maximum poly-γ-glutamic acid yield of 14.08 g·L^(–1)was finally reached with 30 g·L^(–1)glutamate.

Efficient production of poly-γ-glutamic acid by Bacillus velezensis via solid-state fermentation and its application

A novel glutamate-dependent poly-γ-glutamic acid(γ-PGA)-producing strain Bacillus velezensis CAU263 isolated from Chinese traditional Douchi was evaluated.An efficient method ofγ-PGA production was performed by this strain via solid-state fermentation(SSF)using guar meal.The maximal yield ofγ-PGA reached 158.5 g/kg dry weight(DW)in 250 mL flasks and 155.1 g/kg DW in shallow tray,respectively.The molecular weight ofγ-PGA was 3.8×106 Da,the ratio of L/D-glutamic acid was 26.1%and 73.9%.Additionally,γ-PGA significantly improved the operating characteristics of wheat dough,the specific volume of bread was increased by 15.8%and the bread hardness was reduced by 44.2%owing to the addition of 0.3 g/kgγ-PGA.Thus,γ-PGA could be produced by Bacillus velezensis CAU263 at high level using guar meal and might have potential application prospect in food industry.