Sorbate metal complexes as newer antibacterial, antibiofilm, and anticancer compounds.

BACKGROUND: The ineffectiveness of treatments for infections caused by biofilm-producing pathogens and human carcinoma presents considerable challenges for global public health organizations. To tackle this issue, our study focused on exploring the potential of synthesizing new complexes of Co(II), Cu(II), Ni(II), and Zn(II) with sorbic acid to enhance its antibacterial, antibiofilm, and anticancer properties. METHODS: Four novel complexes were synthesized as solid phases by reacting sorbic acid with Co(II), Cu(II), Ni(II), and Zn(II). These complexes were characterized by various technique, including infrared spectra, UV-Visible spectroscopy, proton nuclear magnetic resonance (1H NMR), and thermal analysis techniques, including thermogravimetry (TG). RESULTS: The data acquired from all investigated chemical characterization methods confirmed the chemical structure of the sorbate metal complexes. These complexes exhibited antibacterial and antibiofilm properties against both Gram-positive and Gram-negative bacteria. Furthermore, these complexes enhanced the antibacterial effects of commonly used antibiotics, such as gentamicin and imipenem, with fractional inhibitory concentration (FIC) indices ≤ 0.5. Notably, the Cu(II) complex displayed the most potent antibacterial and antibiofilm activities, with minimum inhibitory concentration (MIC) values of 312.5 µg/mL and 625.0 µg/mL for Bacillus cereus and Escherichia coli, respectively. Additionally, in vitro assays using the methyl thiazolyl tetrazolium (MTT) method showed inhibitory effects on the growth of the human colon carcinoma cell line (HCT-116 cells) following treatment with the investigated metal complexes. The IC50 values for Co(II), Cu(II), Zn(II), and Ni(II) were 3230 µg/mL, 2110 µg/mL, 3730 µg/mL, and 2240 µg/mL, respectively. CONCLUSION: Our findings offer potential for pharmaceutical companies to explore the development of novel combinations involving traditional antibiotics or anticancer drugs with sorbate copper complex.

Molecular docking study of frequently used food additives for selected targets depending on the chromosomal abnormalities they cause.

Food additives (FAs) (flavor enhancers, sweeteners, etc.) protect foods during storage and transportation, making them attractive to consumers. Today, while the desire to access natural foods is increasing, the chemicals added to foods have started to be questioned. In this respect, genotoxicity tests have gained importance. Studies show that some food additives may have genotoxic risks. Previous studies carried out in our laboratory also revealed genotoxic effects of Monopotassium glutamate (MPG), Monosodium glutamate (MSG), Magnesium diglutamate (MDG) as flavor enhancers; Potassium benzoate (PB), Potassium sorbate (PS), Sodium benzoate (SB), Sodium sorbate (SS) as preservatives; Acesulfame potassium (ACE-K), Xylitol (XYL) as sweeteners. In this study, we determined the interactions of these food additives with ATM and p53 proteins, which are activated in the cell due to genotoxic effects, and with DNA by employing the molecular docking method for the first time. Among the food additives, SB (-4.307) for ATM, XYL (-4.629) for p53, and XYL (-4.927) for DNA showed the highest affinity. Therefore, flexible docking (IFD) scores were determined for SB, XYL, and MDG from flavor enhancers. The potential binding modes of the food additives to target molecules' possible inhibition mechanisms were determined by molecular docking. Thus, new information was obtained to show how these additives cause chromosomal abnormalities.

An integrated yeast-based process for cis,cis-muconic acid production.

Cis,cis-muconic acid (CCM) is a promising polymer building block. CCM can be made by whole-cell bioconversion of lignin hydrolysates or de novo biosynthesis from sugar feedstocks using engineered microorganisms. At present, however, there is no established process for large-scale CCM production. In this study, we developed an integrated process for manufacturing CCM from glucose by yeast fermentation. We systematically engineered the CCM-producing Saccharomyces cerevisiae strain by rewiring the shikimate pathway flux and enhancing phosphoenolpyruvate supply. The engineered strain ST10209 accumulated less biomass but produced 1.4 g/L CCM (70 mg CCM per g glucose) in microplate assay, 71% more than the previously engineered strain ST8943. The strain ST10209 produced 22.5 g/L CCM in a 2 L fermenter with a productivity of 0.19 g/L/h, compared to 0.14 g/L/h achieved by ST8943 in our previous report under the same fermentation conditions. The fermentation process was demonstrated at pilot scale in 10 and 50 L steel tanks. In 10 L fermenter, ST10209 produced 20.8 g/L CCM with a CCM yield of 0.1 g/g glucose and a productivity of 0.21 g/L/h, representing the highest to-date CCM yield and productivity. We developed a CCM recovery and purification process by treating the fermentation broth with activated carbon at low pH and low temperature, achieving an overall CCM recovery yield of 66.3% and 95.4% purity. In summary, we report an integrated CCM production process employing engineered S. cerevisiae yeast.

Assessment of Concentrated Liquid Coffee Acceptance during Storage: Sensory and Physicochemical Perspective.

Concentrated liquid coffees (CLCs) refer to stored extracts stable at environmental temperature, used as ingredients in the retail market. Their low chemical stability affects the sensory profile. This study was performed in two CLCs, one without additives (BIB) and another with a mix of sodium benzoate and potassium sorbate additives (SD), stored at 25 °C for one year. Quantitative-Descriptive (QDA) and discriminant analyses permitted identifying the critical sensory attributes and their evolution over time. The concentrate without additives presented an acceptance limit of 196 days (evaluated at a 50% acceptance ratio), while the additives increased the shelf life up to 226 days (38.9% improvement). The rejection was related to a decreased aroma, increased acidity, and reduced bitterness. A bootstrapped feature selection version of Partial Least Square analysis further demonstrated that reactions of 5-caffeoylquinic acid (5CQA) and 3,5-dicaffeoylquinic acid (3,5diCQA) could cause changes in the aroma at the first degradation stage. In the following stages, changes in fructose and stearic acid contents, a key indicator of acceptance for both extracts possibly related to non-enzymatic reactions involving fructose and other compounds, might affect the bitterness and acidity. These results provided valuable information to understand flavor degradation in CLCs.

Engineering an Optogenetic CRISPRi Platform for Improved Chemical Production.

Microbial synthesis of chemicals typically requires the redistribution of metabolic flux toward the synthesis of targeted products. Dynamic control is emerging as an effective approach for solving the hurdles mentioned above. As light could control the cell behavior in a spatial and temporal manner, the optogenetic-CRISPR interference (opto-CRISPRi) technique that allocates the metabolic resources according to different optical signal frequencies will enable bacteria to be controlled between the growth phase and the production stage. In this study, we applied a blue light-sensitive protein EL222 to regulate the expression of the dCpf1-mediated CRISPRi system that turns off the competitive pathways and redirects the metabolic flux toward the heterologous muconic acid synthesis in Escherichia coli. We found that the opto-CRISPRi system dynamically regulating the suppression of the central metabolism and competitive pathways could increase the muconic acid production by 130%. These results demonstrated that the opto-CRISPRi platform is an effective method for enhancing chemical synthesis with broad utilities.

A Nanoprobe Based on Gated Mesoporous Silica Nanoparticles for The Selective and Sensitive Detection of Benzene Metabolite t,t-Muconic Acid in Urine.

Benzene is a highly toxic aromatic hydrocarbon. Inhaling benzene can cause dizziness, vertigo, headaches, aplasia, mutations and, in the most extreme cases, cancer. Trans,trans-muconic acid (t,t-MA) is one of the metabolization products of benzene. Although different analytical methods have been reported for the determination of t,t-MA, these are often expensive, require trained personnel, are not suitable for on-site measurements, and use hazardous organic solvents. For these reasons, the development of reliable, selective and sensitive methods for rapid and in situ detection of t,t-MA are of importance. Addressing this challenge, a nanodevice for the selective and sensitive quantification of t,t-MA in urine is reported. The nanodevice used is achieved using mesoporous silica nanoparticles loaded with a dye reporter and capped with a dicopper(II) azacryptand. Pore opening and payload release is induced rapidly (10 min) and selectively with t,t-MA in urine, using a simple fluorimeter without sample pretreatment.

Properties and Application of Multifunctional Composite Polypropylene-Based Films Incorporating a Combination of BHT, BHA and Sorbic Acid in Extending Donut Shelf-Life.

To extend the shelf-life of packaged donut without the addition of preservative, polypropylene-based active composite films loaded with a combination of sorbic acid, BHA and BHT were prepared by the extrusion moulding method: T1 (Control-pure PP-film), T2 (PP-BHT1%-SA2%), T3 (PP-BHA3%-SA2%) and T4 (PP-BHT1%-BHA1%-SA2%). The incorporation of active additives enhanced water vapour permeability (WVP) and increased oxygen permeability of films. Active films had higher antioxidant activity than pure PP in the order T4 > T2 > T3 (89.11, 83.40 and 79.16%). In vitro examinations demonstrated a significant antibacterial effect on Escherichia coli and S. aureus growth. Overall migration was not significantly different for watery food simulants, while in acidic and fatty foods increased it significantly. The effect of the active films on the fried and packaged donut samples showed significantly higher moisture contents and peroxide values, while acidity was lower. T2 film is proposed due to the preservation of the intrinsic properties of the film, increasing the storage period up to 25 to 50 days.

Recent Advances in Microbial Production of cis,cis-Muconic Acid.

cis,cis-Muconic acid (MA) is a valuable C6 dicarboxylic acid platform chemical that is used as a starting material for the production of various valuable polymers and drugs, including adipic acid and terephthalic acid. As an alternative to traditional chemical processes, bio-based MA production has progressed to the establishment of de novo MA pathways in several microorganisms, such as Escherichia coli, Corynebacterium glutamicum, Pseudomonas putida, and Saccharomyces cerevisiae. Redesign of the metabolic pathway, intermediate flux control, and culture process optimization were all pursued to maximize the microbial MA production yield. Recently, MA production from biomass, such as the aromatic polymer lignin, has also attracted attention from researchers focusing on microbes that are tolerant to aromatic compounds. This paper summarizes recent microbial MA production strategies that involve engineering the metabolic pathway genes as well as the heterologous expression of some foreign genes involved in MA biosynthesis. Microbial MA production will continue to play a vital role in the field of bio-refineries and a feasible way to complement various petrochemical-based chemical processes.

Effects of a chemical additive on the fermentation, microbial communities, and aerobic stability of corn silage with or without air stress during storage.

We evaluated the effects of a chemical additive on the microbial communities, fermentation profile, and aerobic stability of whole-plant corn silage with or without air stress during storage. Whole-plant corn was either untreated or treated with a chemical additive containing sodium benzoate, potassium sorbate, and sodium nitrite at 2 or 3 liters/t of fresh forage weight. Ten individually treated and replicated silos (7.5 liters) were made for each treatment. Half of the silos remained sealed throughout a 63-d storage period, and the other half was subjected to air stress for 2 h/wk. The composition of the bacterial and fungal communities of fresh forage and silages untreated or treated with 2 liters/t of fresh forage weight was analyzed by Illumina Miseq sequencing. Treated silage had greater (P < 0.05) aerobic stability than untreated, even when subjected to air stress during storage, but the numbers of yeasts culturable on selective agar were not affected. However, the additive reduced the relative abundance (RA) of the lactating-assimilating yeast Candida tropicalis (P < 0.01). In air-stressed silages, untreated silage had a greater (P < 0.05) RA of Pichia kudriavzevii (also a lactate assimilator) than treated silage, whereas treated silage was dominated by Candida humilis, which is usually unable to assimilate lactate or assimilates it slowly. The additive improved the aerobic stability by specifically preventing the dominance of yeast species that can consume lactate and initiate aerobic spoilage. To the best of our knowledge, this is the first work that identifies the specific action of this additive on shifting the microbial communities in corn silage.

Cyclodextrin-grafted nanoparticles as food preservative carriers.

Photocatalytic properties of titanium dioxide nanoparticles (TiO2 NPs) have encouraged their use as fillers in polymer-based nanocomposites for application in food packaging. The surface modification of TiO2 NPs with cyclodextrins (CDs) can improve their functionality in a large extent. With this purpose, sorbic acid (SA) and benzoic acid (BA), commonly used as antifungal and antibacterial food preservatives, respectively, have been encapsulated in CD-grafted NPs. Inclusion complex formation of SA and BA with α and ßCDs in water has been assessed first by means of 1H NMR and UV-Vis spectroscopy to determine the affinity of the preservatives for the macrocycles and the stoichiometry of the complexes. The association constants of both preservatives were found to be lower for ßCD, however, the loading efficiency in ßCD-grafted NPs was higher than that exhibited by αCD-NPs. Release kinetics from the CD-grafted NPs have been carried out. In the case of SA, the αCD-grafted NPs showed a prolonged and sustained release profile, suggesting its application as microbial growth inhibition system if incorporated into packaging materials.

Synthesis, characterization and antibacterial properties of novel cellulose acetate sorbate.

In this paper, cellulose acetate (CA) with different degree of substitution (DS) of 2.17∼1.75 were obtained through hydrolysis of cellulose diacetate (CDA). Furthermore, novel cellulose acetate sorbate (CASA) were synthesized by esterification of CA and sorbic acid (SA). The DS of sorbyl groups varied within 0.12-1.20 by adjusting composition ratio, reaction time and temperature. Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (NMR) and elemental analysis were used to determine the chemical structure. Scanning electron microscopy (SEM) indicated CASA showed denser surface morphology than CA. Thermal properties and crystallization of CASA were slightly decrease but did not affect their service performance. Specifically, all CASA showed excellent antibacterial ability, the maximum relative bactericidal rate reached 81.5 % for Escherichia coli (E. coli) and 95.4 % for Staphylococcus aureus (S. aureus), respectively. Moreover, the obtained CASA films using casting technique possessed good mechanical properties. These antibacterial CASA exhibited potential application in healthcare fields.

Bioprivileged Molecules: Integrating Biological and Chemical Catalysis for Biomass Conversion.

Further development of biomass conversions to viable chemicals and fuels will require improved atom utilization, process efficiency, and synergistic allocation of carbon feedstock into diverse products, as is the case in the well-developed petroleum industry. The integration of biological and chemical processes, which harnesses the strength of each type of process, can lead to advantaged processes over processes limited to one or the other. This synergy can be achieved through bioprivileged molecules that can be leveraged to produce a diversity of products, including both replacement molecules and novel molecules with enhanced performance properties. However, important challenges arise in the development of bioprivileged molecules. This review discusses the integration of biological and chemical processes and its use in the development of bioprivileged molecules, with a further focus on key hurdles that must be overcome for successful implementation.

Improvement of cis,cis-Muconic Acid Production in Saccharomyces cerevisiae through Biosensor-Aided Genome Engineering.

Muconic acid is a potential platform chemical for the production of nylon, polyurethanes, and terephthalic acid. It is also an attractive functional copolymer in plastics due to its two double bonds. At this time, no economically viable process for the production of muconic acid exists. To harness novel genetic targets for improved production of cis,cis-muconic acid (CCM) in the yeast Saccharomyces cerevisiae, we employed a CCM-biosensor coupled to GFP expression with a broad dynamic response to screen UV-mutagenesis libraries of CCM-producing yeast. Via fluorescence activated cell sorting we identified a clone Mut131 with a 49.7% higher CCM titer and 164% higher titer of biosynthetic intermediate-protocatechuic acid (PCA). Genome resequencing of the Mut131 and reverse engineering identified seven causal missense mutations of the native genes (PWP2, EST2, ATG1, DIT1, CDC15, CTS2, and MNE1) and a duplication of two CCM biosynthetic genes, encoding dehydroshikimate dehydratase and catechol 1,2-dioxygenase, which were not recognized as flux controlling before. The Mut131 strain was further rationally engineered by overexpression of the genes encoding for PCA decarboxylase and AROM protein without shikimate dehydrogenase domain (Aro1pΔE), and by restoring URA3 prototrophy. The resulting engineered strain produced 20.8 g/L CCM in controlled fed-batch fermentation, with a yield of 66.2 mg/g glucose and a productivity of 139 mg/L/h, representing the highest reported performance metrics in a yeast for de novo CCM production to date and the highest production of an aromatic compound in yeast. The study illustrates the benefit of biosensor-based selection and brings closer the prospect of biobased muconic acid.

Microbial biotransformation of N-nitro-, C-nitro-, and C-nitrous-type mutagens by Lactobacillus delbrueckii subsp. bulgaricus in meat products.

Processed meats are classified by the International Agency for Research on Cancer (IARC) as carcinogenic to humans. However, information on the responsible agents and the influence of industrial processing on the increased risk of cancer is still lacking. This study aimed to use cultures of Lactobacillus delbrueckii subsp. bulgaricus LB-UFSC 01 to biodegrade harmful C-nitrous, N-nitro, and C-nitro compounds in processed meat matrix. Firstly, positive results for ethylnitrolic acid (ENA) (>5.00 µg kg-1) and 2-methyl-1,4-dinitro-pyrrole (DNMP) (>12.0 µg kg-1) were obtained in mortadellas produced under different experimental conditions employing preservatives and antioxidants. Mortadellas containing nitrite and sorbate in the ratio of 8:1 (w/w) yielded the highest concentrations of mutagens. However, the treatment with the LB-UFSC 01 culture was able to modulate the harmful compounds in the mortadella samples. Several analytical methods employing liquid chromatography coupled to mass spectrometry and statistical models were employed to identify the metabolites and reaction routes during microbial biotransformation. For the first time, relevant information regarding the formation and degradation of ENA and DNMP in a processed meat model simulating real conditions was presented.

Removal of dimethachlon from soils using immobilized cells and enzymes of a novel potential degrader Providencia stuartii JD.

The first potential degrader capable of detoxifying dimethachlon (NDPS) was isolated and identified as Providencia stuartii JD, whose free cells and freely crude enzymes degraded more than 80% and 90% of 50 mg L-1 NDPS in liquid culture within 7 d and 2 h, respectively. Strain JD metabolized NDPS through the typical pathway, in which NDPS was firstly transformed into succinic acid and 3, 5-dichloroanilin, and the latter was then converted to phenol, which was subsequently degraded to muconic acid further subjected to the mineralization. The immobilization obviously improved the stability and adaptability of cells and enzymes. In laboratory non-sterile soils treated by free or immobilized cells and enzymes, 50 mg kg-1 NDPS decreased to 15.66 and 13.32 mg kg-1, or 8.32 and 2.18 mg kg-1 within 7 d, respectively. In field, immobilized cells and enzymes exhibited significantly higher efficiencies in removing 20.250 kg a.i. ha-1 NDPS wettable powder from soils after 9 d (96.02% and 98.56%) than free cells and enzymes (79.35% and 66.45%). This study highlights that strain JD promises the great potential to remove hazardous NDPS residues and its immobilized cells and enzymes possess the more promising advantages in the bioremediation of NDPS-contaminated soils in situ.

Molecular and technical aspects on the interaction of serum albumin with multifunctional food preservatives.

Synthetic food preservatives like sodium acetate (SA), sodium benzoate (SB), potassium sorbate (PS) and Butyl paraben (BP) have been widely used in food and pharmacy industries. One of the toxicological aspects of food additives is evaluation of their interaction with serum proteins such as albumin. These additives interaction with human serum albumin (HSA) can exert considerable effect on the absorption, distribution, metabolism and toxicity of chemical compounds. It should be noticed that the aforementioned food preservatives intake increase mainly in the presence of glucose may lead to complex formation of SA, SB, PS and BP with HSA and accelerate the development of variety disease such as cancer, diabetes, multiple sclerosis, brain damage, nausea and cardiac disease. Therefore, to understand the mechanisms of aforementioned food additives interaction and conformational changes of proteins, we aim to review various studies that investigated albumin interaction with these additives using several procedures.

Effect of Potassium Sorbate and Ultrasonic Treatment on the Properties of Fish Scale Collagen/Polyvinyl Alcohol Composite Film.

Composite films containing different amounts of potassium sorbate (KS) were prepared by using fish scale collagen (Col) and polyvinyl alcohol (PVA). Fourier transform infrared spectroscopy (FTIR), light transmittance, mechanical, water vapor transmission rate (WVTR), and the antibacterial properties of the composite films were analyzed. The results showed that the addition of Col significantly reduced the light transmittance of the composite film, but KS had no significant effect on the light transmission. The tensile strength decreased first and then increased with the addition of KS, while the WVTR increased first and then decreased. The composite film exhibited a certain degree of antibacterial properties against E. coli and S. aureus. In addition, we found that ultrasonic treatment reduced the WVTR, and also improved tensile strength and elongation at break of the composite films, but had no significant effect on other properties. The KS/Col/PVA films have the potential to be used as antimicrobial food packaging.

Naturally occurring benzoic, sorbic, and propionic acid in vegetables.

Benzoic, sorbic and propionic acid are used as preservatives in foods and can also be naturally present in processed foods. The levels of preservatives in 939 vegetables were determined. Benzoic and sorbic acid were analysed by high-performance liquid chromatography with a diode-array detector and further confirmed by liquid chromatography-tandem mass spectrometry, whereas propionic acid was analysed using a gas chromatography-flame ionization detector and further confirmed by gas chromatography-mass spectrometry. Benzoic and propionic acid were found in 10.9% and 36.2%, respectively, of the samples. In contrast, sorbic acid was not found in any of the samples. The highest amounts of benzoic and propionic acid were found in perilla leaves (0.33-298 mg kg-1) and ginseng (

Larvicidal potential of piperovatine in the control of cattle tick.

Rhipicephalus (Boophilus) microplus is one of the most important ectoparasites in cattle breeding worldwide, causing direct and indirect losses to animals and producers. Chemical acaricides are utilized in the control of cattle tick and the increase in the development of resistance by ectoparasites makes new alternative necessary. Therefore, research studies have been carried out using bioactive molecules that are quickly degraded and that reduce poisoning to appliers and non-target organisms, environmental contamination and development of resistance. Thus, this study aimed to isolate piperovatine from the roots of Piper corcovadensis, a native species to Brazil, and to evaluate the larvicidal activity against Rhipicephalus (Boophilus) microplus by larval packet test and in ex situ in an open environment. Piperovatine was isolated by classical column chromatography, and identified by 1H and 13C NMR. The lethal concentration (LC) of piperovatine that killed 50% (LC50) and 99% (LC99) of the larvae was determined by Probit analysis. The results indicated LC50 5.17 and LC99 25.41 µg/mL. LC99 was tested in ex situ in an open environment, and an efficiency of 96.63% was found, indicating that piperovatine kept the larvicidal action determined in in vitro test and in open environment. Therefore, this study shows new perspectives to develop products that can be applied in natural conditions to control this ectoparasite.

Alternatives to carcinogenic preservatives in Chinese Sausage - Sorbic acid-loaded chitosan/tripolyphosphate nanoparticles.

Preservatives in processed meat raise significant concerns associated with bowel cancer and diabetes, and implicate various public health issues. This introduces the need for safer preservatives to uphold public health standards. However, developing safer alternatives to these preservatives poses a significant challenge to food industry. A potential solution to this issue is the use of loaded nanoparticles as preservative agents. This study investigated antimicrobial and antioxidant effects of sorbic acid-loaded chitosan/tripolyphosphate nanoparticles (SAN) in Chinese Sausage. SAN were prepared through ionic gelation, followed by natural air-drying for 20 days. After preparation, the antimicrobial and antioxidant activities of various treatment groups were analyzed intermittently during storage at room temperature. SAN-treated samples had significantly lower levels of surviving bacteria, molds, and yeasts than the blank control (p < 0.05) over the entire 72 days of storage. Additionally the SAN-treated samples also had lower levels of surviving bacteria than the chitosan/tripolyphosphate samples after 31-56 days of storage (p < 0.05). The thiobarbituric acid value and pH of the SAN-treated samples were also significantly lower than the blank control (p < 0.05). These results indicated that SAN could be a good intervention strategy to retard lipid oxidation and inhibit microbial growth in Chinese Sausage.