How to deal with xenobiotic compounds through environment friendly approach?

Every year, a huge amount of lethal compounds, such as synthetic dyes, pesticides, pharmaceuticals, hydrocarbons, etc. are mass produced worldwide, which negatively affect soil, air, and water quality. At present, pesticides are used very frequently to meet the requirements of modernized agriculture. The Food and Agriculture Organization of the United Nations (FAO) estimates that food production will increase by 80% by 2050 to keep up with the growing population, consequently pesticides will continue to play a role in agriculture. However, improper handling of these highly persistent chemicals leads to pollution of the environment and accumulation in food chain. These effects necessitate the development of technologies to eliminate or degrade these pollutants. Degradation of these compounds by physical and chemical processes is expensive and usually results in secondary compounds with higher toxicity. The biological strategies proposed for the degradation of these compounds are both cost-effective and eco-friendly. Microbes play an imperative role in the degradation of xenobiotic compounds that have toxic effects on the environment. This review on the fate of xenobiotic compounds in the environment presents cutting-edge insights and novel contributions in different fields. Microbial community dynamics in water bodies, genetic modification for enhanced pesticide degradation and the use of fungi for pharmaceutical removal, white-rot fungi's versatile ligninolytic enzymes and biodegradation potential are highlighted. Here we emphasize the factors influencing bioremediation, such as microbial interactions and carbon catabolism repression, along with a nuanced view of challenges and limitations. Overall, this review provides a comprehensive perspective on the bioremediation strategies.

Biomanufacturing of glycosylated antibodies: Challenges, solutions, and future prospects.

Traditionally, recombinant protein production has been done in several expression hosts of bacteria, fungi, and majorly CHO (Chinese Hamster Ovary) cells; few have high production costs and are susceptible to harmful toxin contamination. Green algae have the potential to produce recombinant proteins in a more sustainable manner. Microalgal diversity leads to offer excellent opportunities to produce glycosylated antibodies. An antibody with humanized glycans plays a crucial role in cellular communication that works to regulate cells and molecules, to control disease, and to stimulate immunity. Therefore, it becomes necessary to understand the role of abiotic factors (light, temperature, pH, etc.) in the production of bioactive molecules and molecular mechanisms of product synthesis from microalgae which would lead to harnessing the potential of algal bio-refinery. However, the potential of microalgae as the source of bio-refinery has been less explored. In the present review, omics approaches for microalgal engineering, methods of humanized glycoproteins production focusing majorly on N-glycosylation pathways, light-based regulation of glycosylation machinery, and production of antibodies with humanized glycans in microalgae with a major emphasis on modulation of post-translation machinery of microalgae which might play a role in better understanding of microalgal potential as a source for antibody production along with future perspectives.

Understanding resistance acquisition by Pseudomonas aeruginosa and possible pharmacological approaches in palliating its pathogenesis.

Pseudomonas aeruginosa can utilize various virulence factors necessary for host infection and persistence. These virulence factors include pyocyanin, proteases, exotoxins, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), phospholipases, and siderophores that enable the bacteria to cause severe infections in immunocompromised individuals. P. aeruginosa falls into the category of nosocomial pathogens that are typically resistant to available antibiotics and therapeutic approaches. P. aeruginosa bio-film formation is a major concern in hospitals because it can cause chronic infection and increase the risk of mortality. Therefore, the development of new strategies to disrupt biofilm formation and improve antibiotic efficacy for the treatment of P. aeruginosa infections is crucial. Anti-biofilm and anti-quorum sensing (QS) activity can be viewed as an anti-virulence approach to control the infectious nature of P. aeruginosa. Inhibition of QS and biofilm formation can be achieved through pharmacological approaches such as phytochemicals and essential oils, which have shown promising results in laboratory studies. A regulatory protein called LasR plays a key role in QS signaling to coordinate gene expression. Designing an antagonist molecule that mimics the natural autoinducer might be the best approach for LasR inhibition. Here we reviewed the mechanism behind antibiotic resistance and alternative approaches to combat the pathogenicity of P. aeruginosa.

Combining in silico and in vitro approaches to understand the involvement of methylerythritol 4-phosphate and shikimate pathways in Agrobacterium tumefaciens for enhanced coenzyme Q10 production.

AIMS: To perform an integrated comparative analysis of metabolic pathway to understand coenzyme Q10 (CoQ10) production in Agrobacterium tumefaciens. METHODS AND RESULTS: Comparative analysis of the CoQ10 metabolic pathway in 10 organisms using a genome to KEGG orthology program (G2KO) and the KEGG database elucidated the completeness of the production pathway in A. tumefaciens. The specific roles of the key precursors and the enzymes in the metabolic network were subsequently confirmed using pathway inhibitors and enhancers. While the use of fosmidomycin and glyphosate was found to inhibit CoQ10 production by 54.54% to 99%, the supplementation of polyprenyl pyrophosphate of the methylerythritol 4-phosphate pathway and 4-hydroxybenzoate precursor of the shikimate pathway did increse the production of CoQ10 by 2.3-fold. CONCLUSIONS: The present study provides a comprehensive understanding of the CoQ10 biosynthetic pathway in A. tumefaciens, which would assist rational metabolic engineering strategies for augmenting CoQ10 biosynthesis.

Photocatalytic degradation of four emerging antibiotic contaminants and toxicity assessment in wastewater: A comprehensive study.

Excessive usage and unrestricted discharge of antibiotics in the environment lead to their accumulation in the ecosystem due to their highly stable and non-biodegradation nature. Photodegradation of four most consumed antibiotics such as amoxicillin, azithromycin, cefixime, and ciprofloxacin were studied using Cu2O-TiO2 nanotubes. Cytotoxicity evaluation of the native and transformed products was conducted on the RAW 264.7 cell lines. Photocatalyst loading (0.1-2.0 g/L), pH (5, 7 and 9), initial antibiotic load (50-1000 µg/mL) and cuprous oxide percentage (5, 10 and 20) were optimized for efficient photodegradation of antibiotics. Quenching experiments to evaluate the mechanism of photodegradation with hydroxyl and superoxide radicals were found the most reactive species of the selected antibiotics. Complete degradation of selected antibiotics was achieved in 90 min with 1.5 g/L of 10% Cu2O-TiO2 nanotubes with initial antibiotic concentration (100 µg/mL) at neutral pH of water matrix. The photocatalyst showed high chemical stability and reusability up to five consecutive cycles. Zeta potential studies confirms the high stability and activity of 10% C-TAC (Cuprous oxide doped Titanium dioxide nanotubes for Applied Catalysis) in the tested pH conditions. Photoluminescence and Electrochemical Impedance Spectroscopy data speculates that 10% C-TAC photocatalyst have efficient photoexcitation in the visible light for photodegradation of antibiotics samples. Inhibitory concentration (IC50) interpretation from the toxicity analysis of native antibiotics concluded that ciprofloxacin was the most toxic antibiotic among the selected antibiotics. Cytotoxicity percentage of transformed products showed r: -0.985, p: 0.01 (negative correlation) with the degradation percentage revealing the efficient degradation of selected antibiotics with no toxic by-products.

Enhanced Production of Lipstatin Through NTG Treatment of Streptomyces toxytricini KD18 at 5 L Bioreactor Level.

Lipstatin, natural inhibitor of pancreatic lipase produced by Streptomyces toxytricini and used as an anti-obesity drug. Chemical mutagenesis was performed with different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (NTG) for strain improvement to obtain high yield of lipstatin. It was observed that the potential of the wild type strain to produce lipstatin (1.09 g/L) was very low. Selected mutants produced lipstatin in the range of 1.20-2.23 g/L at the flask level where maximum amount of lipstatin was produced by M5 mutant. For comparative study, both the parent and M5 mutant strain of S. toxytricini were grown at the lab scale bioreactor with suitable sources of carbon and nitrogen. Significant increase in the production of lipstatin was observed at the bioreactor level where the wild type strain produced 2.4 g/L of lipstatin, while through the NTG mutation, the production of lipstatin was 5.35 g/L. However, Dry Cell Weight (DCW) of the mutant strain was less in comparison with wild type strain and significant morphological differences were observed. Nearly 5 times increase in the production of lipstatin was achieved through NTG mutation and bioreactor-controlled conditions. It was determined that the NTG treatment might be beneficial for strain improvement to get a better candidate for lipstatin production on commercial scale.

Metal organic framework-derived recyclable magnetic coral Co@Co3O4/C for adsorptive removal of antibiotics from wastewater.

The menace posed by antibiotic contamination to humanity has increased due to the absence of efficient antibiotic removal processes in the conventional waste water treatment methods from the hospitals, households, animal husbandry, and pharma industry. Importantly, only a few commercially available adsorbents are magnetic, porous, and have the ability to selectively bind and separate various classes of antibiotics from the slurries. Herein, we report the synthesis of a coral-like Co@Co3O4/C nanohybrid for the remediation of three different classes of antibiotics - quinolone, tetracycline, and sulphonamide. The coral like Co@Co3O4/C materials are synthesized via a facile room temperature wet chemical method followed by annealing in a controlled atmosphere. The materials demonstrate an attractive porous structure with an excellent surface-to-mass ratio of 554.8 m2 g-1 alongside superior magnetic responses. A time-varying adsorption study of aqueous nalidixic acid solution on Co@Co3O4/C nanohybrids indicates that these coral-like Co@Co3O4/C nanohybrids could achieve a high removal efficiency of 99.98% at pH 6 in 120 min. The adsorption kinetics data of Co@Co3O4/C nanohybrids follow a pseudo-second-order reaction kinetics suggesting a chemisorption effect. The adsorbent has also shown its merit in reusability for four adsorption-desorption cycles without showing significant change in the removal efficiency. More in-depth studies validate that the excellent adsorption capability of Co@Co3O4/C adsorbent attributing to the electrostatic and π-π interaction between adsorbent and various antibiotics. Concisely, the adsorbent manifests the potential for the removal of a wide range of antibiotics from the water alongside showing their utility in the hassle-free magnetic separation.

Draft genome sequence of Streptomyces sp. KD18, isolated from industrial soil.

The present study scrutinizes the presence of Streptomyces strains in the soil sample collected from industrial area of Bahadurgarh (Haryana) India. The morphological approach manifested the isolated strain belong to Streptomyces species and named as Streptomyces sp. KD18. Sequencing of Streptomyces sp. KD18 genome was performed by Illumina Nextseq500 platform. 65 contigs were generated via SPAdes v3.11.1 and harboured genome size of 7.2 Mb. AntiSMASH server revealed the presence of 25 biosynthetic gene clusters in KD18 genome where BGC of lipstatin was of more interest from industrial and pharmaceutical purpose. The draft genome sequence represented via ANI values claimed that the KD18 strain belongs to Streptomyces toxytricini and finally named as S. toxytricini KD18. The LC-MS analysis of the extracted metabolite confirmed the production of lipstatin. The genome sequence data have been deposited to NCBI under the accession number of GCA_014748315.1. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03453-3.

Multiomics and optobiotechnological approaches for the development of microalgal strain for production of aviation biofuel and biorefinery.

Demand and consumption of fossil fuels is increasing daily, and oil reserves are depleting. Technological developments are required towards developing sustainable renewable energy sources and microalgae are emerging as a potential candidate for various application-driven research. Molecular understanding attained through omics and system biology approach empowering researchers to modify various metabolic pathways of microalgal system for efficient extraction of biofuel and important biomolecules. This review furnish insight into different "advanced approaches" like optogenetics, systems biology and multi-omics for enhanced production of FAS (Fatty Acid Synthesis) and lipids in microalgae and their associated challenges. These new approaches would be helpful in the path of developing microalgae inspired technological platforms for optobiorefinery, which could be explored as source material to produce biofuels and other valuable bio-compounds on a large scale.

Visible-Light-Driven Photocatalytic Degradation of Tetracycline Using Heterostructured Cu2O-TiO2 Nanotubes, Kinetics, and Toxicity Evaluation of Degraded Products on Cell Lines.

This study first reports on the tetracycline photodegradation with the synthesized heterostructured titanium oxide nanotubes coupled with cuprous oxide photocatalyst. The large surface area and more active sites on TiO2 nanotubes with a reduced band gap (coupling of Cu2O) provide faster photodegradation of tetracycline under visible light conditions. Cytotoxicity experiments performed on the RAW 264.7 (mouse macrophage) and THP-1 (human monocytes) cell lines of tetracycline and the photodegraded products of tetracycline as well as quenching experiments were also performed. The effects of different parameters like pH, photocatalyst loading concentration, cuprous oxide concentration, and tetracycline load on the photodegradation rate were investigated. With an enhanced surface area of nanotubes and a reduced band gap of 2.58 eV, 1.5 g/L concentration of 10% C-TAC showed the highest efficiency of visible-light-driven photodegradation (∼100% photodegradation rate in 60 min) of tetracycline at pH 5, 7, and 9. The photodegradation efficiency is not depleted up to five consecutive batch cycles. Quenching experiments confirmed that superoxide radicals and hydroxyl radicals are the most involved reactive species in the photodegradation of tetracycline, while valance band electrons are the least involved reactive species. The cytotoxicity percentage of tetracycline and its degraded products on RAW 264.7 (-0.932) as well as THP-1 (-0.931) showed a negative correlation with the degradation percentage with a p-value of 0.01. The toxicity-free effluent of photodegradation suggests the application of the synthesized photocatalyst in wastewater treatment.

Valorization of wastewater to recover value-added products: A comprehensive insight and perspective on different technologies.

In recent years, due to rapid globalization and urbanization, the demand for fuels, energy, water and nutrients has been continuously increasing. To meet the future need of the society, wastewater is a prominent and emerging source for resource recovery. It provides an opportunity to recover valuable resources in the form of energy, fertilizers, electricity, nutrients and other products. The aim of this review is to elaborate the scientific literature on the valorization of wastewater using wide range of treatment technologies and reduce the existing knowledge gap in the field of resource recovery and water reuse. Several versatile, resilient environmental techniques/technologies such as ion exchange, bioelectrochemical, adsorption, electrodialysis, solvent extraction, etc. are employed for the extraction of value-added products from waste matrices. Since the last two decades, valuable resources such as polyhydroxyalkanoate (PHA), matrix or polymers, cellulosic fibers, syngas, biodiesel, electricity, nitrogen, phosphorus, sulfur, enzymes and a wide range of platform chemicals have been recovered from wastewater. In this review, the aspects related to the persisting global water issues, the technologies used for the recovery of different products and/or by-products, economic sustainability of the technologies and the challenges encountered during the valorization of wastewater are discussed comprehensively.

TiO2 based Photocatalysis membranes: An efficient strategy for pharmaceutical mineralization.

Among the various emerging contaminants, pharmaceuticals (PhACs) seem to have adverse effects on the quality of water. Even the smallest concentration of PhACs in ground water and drinking water is harmful to humans and aquatic species. Among all the deaths reported due to COVID-19, the mortality rate was higher for those patients who consumed antibiotics. Consequently, PhAC in water is a serious concern and their removal needs immediate attention. This study has focused on the PhACs' degradation by collaborating photocatalysis with membrane filtration. TiO2-based photocatalytic membrane is an innovative strategy which demonstrates mineralization of PhACs as a safer option. To highlight the same, an emphasis on the preparation and reinforcing properties of TiO2-based nanomembranes has been elaborated in this review. Further, mineralization of antibiotics or cytostatic compounds and their degradation mechanisms is also highlighted using TiO2 assisted membrane photocatalysis. Experimental reactor configurations have been discussed for commercial implementation of photoreactors for PhAC degradation anchored photocatalytic nanomembranes. Challenges and future perspectives are emphasized in order to design a nanomembrane based prototype in future for wastewater management.

Decentralized systems for the treatment of antimicrobial compounds released from hospital aquatic wastes.

In many developing countries, untreated hospital effluents are discharged and treated simultaneously with municipal wastewater. However, if the hospital effluents are not treated separately, they pose concerning health risks due to the possible transport of the antimicrobial genes and microbes in the environment. Such effluent is considered as a point source for a number of potentially infectious microorganisms, waste antimicrobial compounds and other contaminants that could promote antimicrobial resistance development. The removal of these contaminants prior to discharge reduces the exposure of antimicrobials to the environment and this should lower the risk of superbug development. At an effluent discharge site, suitable pre-treatment of wastewater containing antimicrobials could maximise the ecological impact with potentially reduced risk to human health. In addressing these points, this paper reviews the applications of decentralized treatment systems toward reducing the concentration of antimicrobials in wastewater. The most commonly used techniques in decentralized wastewater treatment systems for onsite removal of antimicrobials were discussed and evidence suggests that hybrid techniques should be more useful for the efficient removal of antimicrobials. It is concluded that alongside the cooperation of administration departments, health industries, water treatment authorities and general public, decentralized treatment technology can efficiently enhance the removal of antimicrobial compounds, thereby decreasing the concentration of contaminants released to the environment that could pose risks to human and ecological health due to development of antimicrobial resistance in microbes.

Whole-Cell Vaccine Preparation: Options and Perspectives.

Vaccines are biological preparations to elicit a specific immune response in individuals against the targetted microorganisms. The use of vaccines has caused the near eradication of many critical diseases and has had an everlasting impact on public health at a relatively low cost. Most of the vaccines developed today are based on techniques which were developed a long time ago. In the beginning, vaccines were prepared from tissue fluids obtained from infected animals or people, but at present, the scenario has changed with the development of vaccines from live or killed whole microorganisms and toxins or using genetic engineering approaches. Considerable efforts have been made in vaccine development, but there are still many diseases that need attention, and new technologies are being developed in vaccinology to combat them. In this chapter, we discuss different approaches for vaccine development, including the properties and preparation of whole-cell vaccines.

Threat and sustainable technological solution for antineoplastic drugs pollution: Review on a persisting global issue.

In the past 20 years, the discharge of pharmaceuticals and their presence in the aquatic environment have been continuously increasing and this has caused serious public health and environmental concerns. Antineoplastic drugs are used in chemotherapy, in large quantities worldwide, for the treatment of continuously increasing cancer cases. Antineoplastic drugs also contaminate water sources and possess mutagenic, cytostatic and eco-toxicological effects on microorganisms present in the aquatic environment as well as on human health. Due to the recalcitrant nature of antineoplastic drugs, the commonly used wastewater treatment processes are not able to eliminate these drugs. Globally, various anticancer drugs are being consumed during chemotherapy in hospitals and households by out-patients. These anti-cancer agents enter the water bodies in their original form or as metabolites via urine and faeces of the out-patients or the patients admitted in hospitals. Due to its high lipid solubility, the antineoplastic drugs accumulate in the fatty tissues of the organisms. These drugs enter through the food chain and cause adverse health effects on humans due to their cytotoxic and genotoxic properties. The United States Environmental Protection Agency (US-EPA) and the Organization for Economic Cooperation and Development (OECD) elucidated new regulations for the management of hazardous pharmaceuticals in the water environment. In this paper, the role of antineoplastic agents as emerging water contaminants, its transfer through the food chain, its eco-toxicological properties and effects, technological solutions and management aspects were reviewed.

In Vitro Cytotoxicity Study of Cyclophosphamide, Etoposide and Paclitaxel on Monocyte Macrophage Cell Line Raw 264.7.

The presence of antineoplastic compounds in aquatic ecosystem is an emerging challenge for the society. Antineoplastic compounds released into the aquatic environment exhibit a potential threat to normal aquatic life. Particularly, antineoplastic compounds are responsible for direct or indirect interference with the cellular DNA of an organism and cause toxicity to cells. The present study focused on the assessment of in vitro toxic effect of cyclophosphamide, etoposide and paclitaxel on Raw 264.7 cell line (mouse monocyte macrophage cells). The inhibitory concentration of cyclophosphamide, etoposide, and paclitaxel was determined. The IC50 values of these compounds were 145.44, 5.40, and 69.76 µg ml-1 respectively. This is the first report on toxicity analysis of cyclophosphamide, paclitaxel and etoposide on Raw 264.7 cell line by reducing cell viability and indicating the cell cytotoxicity i.e., 69.58% for cyclophosphamide, 92.01% for etoposide and 88.85% for paclitaxel on concentration 250 µg ml-1. The results of their cytotoxicity assessment highlight the need of improvement in sewage treatment technology for the efficient removal of these compounds from aquatic environment.

The Interaction of the Microtubule Targeting Anticancer Drug Colchicine with Human Glutathione Transferases.

BACKGROUND: Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that have been shown to be involved in the development of multi-drug resistance (MDR) mechanism toward chemotherapeutic agents. GST inhibitors have, therefore, emerged as promising chemosensitizers to manage and reverse MDR. Colchicine (COL) is a classical antimitotic, tubulin-binding agent (TBA) which is being explored as anticancer drug. METHODS: In the present work, the interaction of COL and its derivative 2,3-didemethylcolchicine (2,3-DDCOL) with human glutathione transferases (hGSTA1-1, hGSTP1-1, hGSTM1-1) was investigated by inhibition analysis, molecular modelling and molecular dynamics simulations. RESULTS: The results showed that both compounds bind reversibly to human GSTs and behave as potent inhibitors. hGSTA1-1 was the most sensitive enzyme to inhibition by COL with IC50 22 µΜ. Molecular modelling predicted that COL overlaps with both the hydrophobic (H-site) and glutathione binding site (G-site) and polar interactions appear to be the driving force for its positioning and recognition at the binding site. The interaction of COL with other members of GST family (hGSTA2-2, hGSTM3-3, hGSTM3-2) was also investigated with similar results. CONCLUSION: The results of the present study might be useful in future drug design and development efforts towards human GSTs.

Enhanced production of lipstatin from mutant of Streptomyces toxytricini and fed-batch strategies under submerged fermentation.

Streptomyces toxytricini produces bioactive metabolite recognized as lipstatin and its intermediate orlistat. The main focus of this study is to enhance lipstatin production by strain improvement and precursor feeding. In this study, strain improvement to enhance the production of lipstatin was carried out by different doses (50, 100, 150, 200, and 250 Gy) of gamma radiation and precursors (Linoleic acid, Oleic acid, and l-Leucine). Screening showed that the highest yield of lipstatin (4.58 mg/g) was produced by mutant designated as SRN 7. The production of lipstatin (5.011 mg/g) increased significantly when the medium was supplemented with ratio 1:1.5 (linoleic acid + oleic acid). The addition of 1.5% l-Leucine leads to further increment in the production of lipstatin (5.765 mg/g). The addition of 10% soy flour in the culture medium resulted in the maximum production of lipstatin to 5.886 mg/g.

Improved Pullulan Production and Process Optimization Using Novel GA-ANN and GA-ANFIS Hybrid Statistical Tools.

Pullulan production from Aureobasidiumpullulans was explored to increase yield. Non-linear hybrid mathematical tools for optimization of process variables as well as the pullulan yield were analyzed. The one variable at a time (OVAT) approach was used to optimize the maximum pullulan yield of 35.16 ± 0.29 g/L. The tools predicted maximum pullulan yields of 39.4918 g/L (genetic algorithm coupled with artificial neural network (GA-ANN)) and 36.0788 g/L (GA coupled with adaptive network based fuzzy inference system (GA-ANFIS)). The best regression value (0.94799) of the Levenberg-Marquardt (LM) algorithm for ANN and the epoch error (6.1055 × 10-5) for GA-ANFIS point towards prediction precision and potentiality of data training models. The process parameters provided by both the tools corresponding to their predicted yield were revalidated by experiments. Among the two of them GA-ANFIS results were replicated with 98.82% accuracy. Thus GA-ANFIS predicted an optimum pullulan yield of 36.0788 g/L with a substrate concentration of 49.94 g/L, incubation period of 182.39 h, temperature of 27.41 °C, pH of 6.99, and agitation speed of 190.08 rpm.