Browsing by Author "Singh, Prashant R."
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Publication Anticancer Compounds from Cyanobacteria and their Implications in Apoptosis(Bentham Science Publishers, 2023) Gupta, Amit; Singh, Prashant R.; Singh, Ashish P.; Kumari, Neha; Jaiswal, Jyoti; Sahu, Niharika; Mishra, Sonal; Pathak, Jainendra; Sinha, Rajeshwar P.Cyanobacteria have been recognized as a rich source of bioactive metabolites with potential biotechnological applications in the pharmacological industry. The chemically diverse natural compounds or their analogues cause cytotoxicity. They may kill various cancer cells by inducing apoptosis or changing the activation of cell signaling, particularly involving the protein kinase-C family of en-zymes, mitochondrial dysfunctions, and oxidative damage. B cell lymphoma 2 (Bcl-2) is an essential component of apoptosis and is an antiapoptotic molecule. The key apoptotic regulators associated with cancer are members of the Bcl-2 protein family, the key member of which is Bcl-2. The Bcl-2 protein is a promising target for the emergence of new anti-tumor therapies because of its critical role in con-trolling apoptosis. This review explores the significance of Bcl-2 in the onset of cancer; it may be used as a target for developing high-quality drug therapies to treat various tumors. In addition, a number of computational techniques were used to identify novel hit compounds that may act as inhibitors of the apoptotic protein Bcl-2, including virtual screening, toxicity prediction, and drug-likeness analysis. Twenty-three compounds were assessed as potential hits against Bcl-2, and these compounds were subjected to ADMET property prediction. Dendroamide A and Welwitindolinone A appear to be the most stable and effective drugs against Bcl-2 out of all those evaluated. This article gives an overview of the bioactive compounds produced by cyanobacteria that have anticancer properties and may be exploited to create novel anticancer medications in the future. � 2023 Bentham Science Publishers.Publication Application of Synthetic Biology Approaches to High-Yield Production of Mycosporine-like Amino Acids(Multidisciplinary Digital Publishing Institute (MDPI), 2023) Singh, Varsha K.; Jha, Sapana; Rana, Palak; Gupta, Amit; Singh, Ashish P.; Kumari, Neha; Mishra, Sonal; Singh, Prashant R.; Jaiswal, Jyoti; Sinha, Rajeshwar P.Ultraviolet (UV) radiation reaching the Earth�s surface is a major societal concern, and therefore, there is a significant consumer demand for cosmetics formulated to mitigate the harmful effects of UV radiation. Synthetic sunscreens being formulated to block UV penetration include inorganic metal oxide particles and organic filters. Lately, organic UV-absorbing compounds are manufactured from non-renewable petrochemicals and, as a result, there is a need to develop a sustainable manufacturing process for efficient, high-level production of a naturally occurring group of UV-absorbing compounds, namely mycosporine-like amino acids (MAAs), for use as a sunscreen additive to skincare products. Currently, the commercial production of MAAs for use in sunscreens is not a viable proposition due to the low yield and the lack of fermentation technology associated with native MAA-producing organisms. This review summarizes the biochemical properties of MAAs, the biosynthetic gene clusters and transcriptional regulations, the associated carbon-flux-driving processes, and the host selection and biosynthetic strategies, with the aim to expand our understanding on engineering suitable cyanobacteria for cost-effective production of natural sunscreens in future practices. � 2023 by the authors.Publication Bioprospecting and Evolutionary Significance of Photoprotectors in Non-flowering Lower Plants(Springer Nature, 2023) Gupta, Amit; Singh, Ashish P.; Sahu, Niharika; Jaiswal, Jyoti; Kumari, Neha; Singh, Prashant R.; Sinha, Rajeshwar P.Environmental change as well as the continued increase in UV radiation (UVR; 280�400 nm) has a significant impact on terrestrial and aquatic ecosystems. The majority of sun-exposed species are negatively affected by solar UVR. This may be the strong reason behind the evolution of photoprotectants like phenylpropanoids, flavonoids, mycosporines, scytonemin, mycosporine-like amino acids (MAAs), parietin, xanthophyll, phycobiliproteins etc. It is mainly found in cyanobacteria, algae, fungi, lichens and other non-flowering lower plants. These photoprotectors have their own evolutionary significance. To reduce photochemical damage, carotenoids are being considered as UV-protective additives. Carotenoids are major light-harvesting and photoprotective components of the photosynthetic apparatus, and work as quencher of singlet oxygen species. Many other UV-absorbing compounds are also known for their multifunctional capabilities, such as flavonoids, which have antioxidative and antibacterial potentials. The study of these photoprotectants has resulted in the identification of new sunscreen classes and their distribution throughout various microbes and non-flowering lower plants. These natural photoprotectants play an important role in different forms such as scytonemin and MAAs operate as the third line of defence in cyanobacteria, mycosporines are critical for UV-induced photodamage in fungi. Lichens possess a wide range of primary and secondary metabolites, in which MAAs and parietin have major photoprotective effects. Moreover, these photoprotectants aid in diffusing heat from absorbed radiation without generating reactive oxygen species (ROS). This chapter deals with the evolutionary significance of photoprotectors and their possible modes of action. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.Publication Bioprospection of Photoprotective Compounds from Cyanobacteria(Springer Nature, 2023) Singh, Prashant R.; Singh, Ashish P.; Rajneesh; Gupta, Amit; Sinha, Rajeshwar P.; Pathak, JainendraCyanobacteria are one of the oldest photosynthetic nitrogen fixers of the terrestrial as well as aquatic ecosystems. Cyanobacteria and microalgae produce a large number of secondary metabolites having biomedical, industrial, and biotechnological importance. Due to their presence in vast habitats, cyanobacteria and microalgae were exposed to variety of harsh environmental factors such as salt, desiccation, temperature, heavy metals, and ultraviolet radiation (UVR). In response, cyanobacteria have developed different mechanisms to cope these harsh environmental conditions. Photosynthetic nature of cyanobacteria continuously exposes them to lethal doses of UVR coming with solar radiation which affects their physiology, photosynthetic efficiency, productivity by reactive oxygen species (ROS) generation inside the cell and ultimately leads to cell death. In response to these stresses cyanobacteria have developed different protective mechanisms such as avoidance, enzymatic and non-enzymatic defence system and synthesis of novel secondary metabolites such as mycosporine-like amino acids (MAAs) and scytonemin. MAAs are water-soluble molecules that absorb short wavelength of solar UVR which release the energy in the form of heat. Scytonemin is a small hydrophobic alkaloid pigment present in the extracellular sheath of some cyanobacteria that acts as UVR protectant. Scytonemin and MAAs are highly photostable therefore, they primarily function as UV-screening compounds. They also show antioxidative properties. The capability of cyanobacteria to produce large number of secondary metabolites which serve as natural sunscreens, antibiotic, antifungal, anticancer and antiviral agents make them economically important organisms. These are readily biotechnologically exploitable in the cosmetics and other industrial sectors for the creation of novel medications and drugs. Hence, bioprospection of these photoprotective compounds and other secondary metabolites from cyanobacteria and microalgae becomes crucial. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.Publication Computational studies on photolyase (Phr) proteins of cyanobacteria(Canadian Science Publishing, 2022) Rajneesh; Mondal, Soumila; Pathak, Jainendra; Singh, Prashant R.; Singh, Shailendra P.; Sinha, Rajeshwar P.Photolyases (Phrs) are enzymes that utilize the blue/ultraviolet (UV-A) region of light for repairing UV-induced cyclopyramidine dimers. We studied Phr groups by bioinformatic analyses as well as active-site and structural modeling. Analysis of 238 amino acid sequences from 85 completely sequenced cyanobacterial genomes revealed five classes of Phrs, CPD Gr I, 6-4 Phrs/cryptochrome, Cry-DASH, Fe-S bacteria Phrs, and a group with fewer amino acids (276�385) in length. The distribution of Phr groups in cyanobacteria belonging to the order Synechococcales was found to be influenced by the habitats of the organisms. Class V Phrs are exclusively present in cyanobacteria. Unique motifs and binding sites were reported in groups II and III. The Fe-S protein binding site was only present in group V and the active site residues and putative CPD/6-4PP binding residues are charged amino acids present on the surface of the proteins. The majority of hydrophilic amino acid residues were present on the surface of the Phrs. Sequence analysis confirmed the diverse nature of Phrs, although sequence diversity did not affect the overall three-dimensional structure. Protein�ligand interaction analysis identified novel CPD/6-4PP binding sites on Phrs. This structural information of Phrs can be used for the preparation of efficient Phr-based formulations. � 2021 The Author(s).Publication Evolution and Distribution of Cyanobacteria(Springer Nature, 2022) Pathak, Jainendra; Singh, Prashant R.; Sinha, Rajeshwar P.; Rastogi, Rajesh P.Cyanobacteria are the ancient group of photosynthetic prokaryotes having pronounced variations in their physiological capacities, cellular differentiation strategies, and choice of habitats. They are the inventors of oxygenic photosynthesis on this planet and hence have played a crucial role in the evolution of biodiversity on Earth by gradually changing the atmospheric chemistry to be suitable for the evolution of eukaryotes. This conversion of atmosphere from anaerobic to an aerobic one was started by cyanobacteria through oxygenic photosynthesis, which finally supplied oxygen to the atmosphere for ~1.5 billion years leading to greater diversification of life on the Earth. Cyanobacteria inhabit a wide range of terrestrial and aquatic environments varying from the hot springs to polar region and other extreme environments. Their long-standing evolutionary history might be the reason for their success in acclimatization and sustenance in such diverse habitats. A high tolerance level of free sulfide and low oxygen, tolerance to lethal ultraviolet radiations, and the capacity to use H2S in place of H2O as a photoreductant are some of the various features of cyanobacteria that have aided in supporting their long history on this planet. Still, the picture regarding evolution and diversification of this ecologically and biotechnologically important group of photoautotrophs is not very clear. In this chapter, we present an overview of structural and genomic evolution of cyanobacteria and their distribution in diverse habitats on Earth. � The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.Publication MOLECULAR MECHANISMS AND IMPORTANCE OF CIRCADIAN RHYTHMS IN MICROORGANISMS(Nova Science Publishers, Inc., 2022) Mishra, Sonal; Kumari, Neha; Jaiswal, Jyoti; Singh, Prashant R.; Gupta, Amit; Sahu, Niharika; Sinha, Rajeshwar P.Circadian rhythms regulate the temporal schedules of the cell�s physiology to facilitate customization to environmental alterations per day which is almost ubiquitous. The molecular mechanisms of circadian rhythms in microorganisms are subject to environmental stimuli such as light intensity, temperature, and humidity generated by Earth�s rotation. In the absence of environmental stimuli, how microorganisms maintain 24 h circadian rhythms had been a mystery for a long period. The most comprehensive understanding of how synchronization of microorganisms circadian oscillator with the environment is generated and how information is transmitted from an oscillator to generate bioactivity rhythms is a breakthrough for the improvement of recent and future work. These consequences have changed the view about circadian rhythms. Rhythm differs from a linear model in that it is considered as a collective organization of multidisciplinary elements that are integrated to accelerate and reset the oscillator within the context of the cell. This chapter discusses how this mechanism of circadian rhythms varies in many microorganisms and how it becomes important for microbes. Over the past few years, we have seen numerous advances in the understanding of the molecular mechanisms of circadian rhythms in microorganisms, and this chapter attempts to outline these mechanisms. � 2022 by Nova Science Publishers, Inc.Publication Natural Sun-Screening Compounds and DNA-Repair Enzymes: Photoprotection and Photoaging(MDPI, 2023) Gupta, Amit; Singh, Ashish P.; Singh, Varsha K.; Singh, Prashant R.; Jaiswal, Jyoti; Kumari, Neha; Upadhye, Vijay; Singh, Suresh C.; Sinha, Rajeshwar P.Ultraviolet radiation (UVR) has been scientifically proven to cause skin disorders such as sunburn, skin cancer and the symptoms of chronic exposure. Natural sun screening compounds have recently gained tremendous attention from the cosmetic and cosmeceutical sectors for treating skin disorders such as hyperpigmentation and aging. A wide range of natural UV-absorbing compounds have been used to replace or reduce the number of synthetic sunscreen molecules. One of the primary causes of photoaging is DNA damage, mainly caused by UVR. Photoprotection provided by traditional sunscreens is purely preventative and has no efficacy after DNA damage has been initiated. As a result, the quest for DNA-repair mechanisms that block, reverse, or postpone pathologic processes in UV-exposed skin has stimulated anti-photoaging research and methods to increase the effectiveness of traditional sunscreens. This review summarizes many natural compounds from microalgae, lichens, and plants that have demonstrated potential photoprotection effects against UV radiation-induced skin damage. Furthermore, it offers an overview of current breakthroughs in DNA-repair enzymes utilized in sunscreens and their influence on photoaging. � 2023 by the authors.Publication Phylogenetic distribution, structural analysis and interaction of nucleotide excision repair proteins in cyanobacteria(Elsevier B.V., 2023) Singh, Prashant R.; Gupta, Amit; Rajneesh; Pathak, Jainendra; Sinha, Rajeshwar P.Cyanobacteria are photosynthetic Gram-negative, oxygen evolving prokaryotes with cosmopolitan distribution. Ultraviolet radiation (UVR) and other abiotic stresses result in DNA lesions in cyanobacteria. Nucleotide excision repair (NER) pathway removes the DNA lesions produced by UVR to normal DNA sequence. In cyanobacteria, detailed knowledge about NER proteins is poorly studied. Therefore, we have studied the NER proteins in cyanobacteria. Analyses of 289 amino acids sequence from 77 cyanobacterial species have revealed the presence of a minimum of one copy of NER protein in their genome. Phylogenetic analysis of NER protein shows that UvrD has maximal rate of amino acid substitutions which resulted in increased branch length. The motif analysis shows that UvrABC proteins is more conserved than UvrD, Further, UvrA with UvrB protein interacts with each other and form stable complex which have DNA binding domain on the surface of the complex. UvrB also have DNA binding domain. Positive electrostatic potential was found in the DNA binding region, which is followed by negative and neutral electrostatic potential. Additionally, the surface accessibility values at the DNA strands of T5-T6 dimer binding site were maximal. Protein nucleotide interaction shows the strong binding of T5-T6 dimer with NER proteins of Synechocystis sp. PCC 6803. This process repairs the UV-induced DNA lesions in dark when photoreactivation is inactive. Regulation of NER proteins protect cyanobacterial genome and maintain the fitness of organism under different abiotic stresses. � 2023 Elsevier B.V.Publication Physiological responses of the cyanobacterium Synechocystis sp. PCC 6803 under rhythmic light variations(Springer Nature, 2023) Singh, Prashant R.; Pathak, Jainendra; Rajneesh; Ahmed, Haseen; H�der, Donat-P.; Sinha, Rajeshwar P.Cyanobacteria are challenged by daily fluctuations of light intensities and photoperiod in their natural habitats, which affect the physiology and fitness of cyanobacteria. Circadian rhythms (CRs), an important endogenous process found in all organisms including cyanobacteria, control their physiological activities and helps in coping with 24-h light/dark (LD) cycle. In cyanobacteria, physiological responses under rhythmic ultraviolet radiation (UVR) are poorly studied. Therefore, we studied the changes in photosynthetic pigments, and physiological parameters of Synechocystis sp. PCC 6803 under UVR and photosynthetically active radiation (PAR) of light/dark (LD) oscillations having the combinations of 0, 4:20, 8:16, 12:12, 16:8, 20:4, and 24:24�h. The LD 16:8 enhanced the growth, pigments, proteins, photosynthetic efficiency, and physiology of Synechocystis sp. PCC6803. Continuous light (LL 24) of UVR and PAR exerted negative impact on the photosynthetic pigments, and chlorophyll fluorescence. Significant increase in reactive oxygen species (ROS) resulted in loss of plasma membrane integrity followed by decreased viability of cells. The dark phase played a significant role in Synechocystis�to withstand the�LL 24 under PAR and UVR. This study offers detailed understanding of the physiological responses of the cyanobacterium to changing light environment. � 2023, The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.