scholarly journals Recent Advances in Heterologous Synthesis Paving Way for Future Green-Modular Bioindustries: A Review With Special Reference to Isoflavonoids

2021 ◽  
Vol 9 ◽  
Author(s):  
Moon Sajid ◽  
Shane Ramsay Stone ◽  
Parwinder Kaur
Keyword(s):  
Genetic Factors ◽  
Plant Secondary Metabolites ◽  
Reaction Rates ◽  
Recent Time ◽  
Commercial Application ◽  
Biosynthetic Pathways ◽  
Market Demand ◽  
Metabolism Regulation ◽  
Multiple Signaling

Isoflavonoids are well-known plant secondary metabolites that have gained importance in recent time due to their multiple nutraceutical and pharmaceutical applications. In plants, isoflavonoids play a role in plant defense and can confer the host plant a competitive advantage to survive and flourish under environmental challenges. In animals, isoflavonoids have been found to interact with multiple signaling pathways and have demonstrated estrogenic, antioxidant and anti-oncologic activities in vivo. The activity of isoflavonoids in the estrogen pathways is such that the class has also been collectively called phytoestrogens. Over 2,400 isoflavonoids, predominantly from legumes, have been identified so far. The biosynthetic pathways of several key isoflavonoids have been established, and the genes and regulatory components involved in the biosynthesis have been characterized. The biosynthesis and accumulation of isoflavonoids in plants are regulated by multiple complex environmental and genetic factors and interactions. Due to this complexity of secondary metabolism regulation, the export and engineering of isoflavonoid biosynthetic pathways into non-endogenous plants are difficult, and instead, the microorganisms Saccharomyces cerevisiae and Escherichia coli have been adapted and engineered for heterologous isoflavonoid synthesis. However, the current ex-planta production approaches have been limited due to slow enzyme kinetics and traditionally laborious genetic engineering methods and require further optimization and development to address the required titers, reaction rates and yield for commercial application. With recent progress in metabolic engineering and the availability of advanced synthetic biology tools, it is envisaged that highly efficient heterologous hosts will soon be engineered to fulfill the growing market demand.

scholarly journals A study of deregulated MMR pathways and anticancer potential of curcuma derivatives using computational approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Priyanjali Bhattacharya ◽  
Trupti N. Patel
Keyword(s):  
Mismatch Repair ◽  
Protein Function ◽  
Curcuma Longa ◽  
Signaling Cascades ◽  
Altered Expression ◽  
Anticancer Properties ◽  
Medicinal Properties ◽  
Multiple Signaling

AbstractPlant derived products have steadily gained momentum in treatment of cancer over the past decades. Curcuma and its derivatives, in particular, have diverse medicinal properties including anticancer potential with proven safety as supported by numerous in vivo and in vitro studies. A defective Mis-Match Repair (MMR) is implicated in solid tumors but its role in haematologic malignancies is not keenly studied and the current literature suggests that it is limited. Nonetheless, there are multiple pathways interjecting the mismatch repair proteins in haematologic cancers that may have a direct or indirect implication in progression of the disease. Here, through computational analysis, we target proteins that are involved in rewiring of multiple signaling cascades via altered expression in cancer using various curcuma derivatives (Curcuma longa L. and Curcuma caesia Roxb.) which in turn, profoundly controls MMR protein function. These biomolecules were screened to identify their efficacy on selected targets (in blood-related cancers); aberrations of which adversely impacted mismatch repair machinery. The study revealed that of the 536 compounds screened, six of them may have the potential to regulate the expression of identified targets and thus revive the MMR function preventing genomic instability. These results reveal that there may be potential plant derived biomolecules that may have anticancer properties against the tumors driven by deregulated MMR-pathways.

scholarly journals Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 991
Author(s):  
Melanie S. Matos ◽  
José D. Anastácio ◽  
Cláudia Nunes dos Santos
Keyword(s):  
Biological Activities ◽  
Sesquiterpene Lactones ◽  
Physiological State ◽  
Plant Secondary Metabolites ◽  
Inflammatory Pathways ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Inflammatory Molecules

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure–activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.

scholarly journals Comparative Meta-Analysis of Transcriptomics Data during Cellular Senescence andIn VivoTissue Ageing

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Konstantinos Voutetakis ◽  
Aristotelis Chatziioannou ◽  
Efstathios S. Gonos ◽  
Ioannis P. Trougakos
Keyword(s):  
Oxidative Phosphorylation ◽  
Actin Cytoskeleton ◽  
Focal Adhesion ◽  
Cellular Senescence ◽  
Meta Analysis ◽  
Metabolism Regulation ◽  
Age Related ◽  
Mapk Signalling ◽  
Transcriptomics Data

Several studies have employed DNA microarrays to identify gene expression signatures that mark human ageing; yet the features underlying this complicated phenomenon remain elusive. We thus conducted a bioinformatics meta-analysis on transcriptomics data from human cell- and biopsy-based microarrays experiments studying cellular senescence orin vivotissue ageing, respectively. We report that coregulated genes in the postmitotic muscle and nervous tissues are classified into pathways involved in cancer, focal adhesion, actin cytoskeleton, MAPK signalling, and metabolism regulation. Genes that are differentially regulated during cellular senescence refer to pathways involved in neurodegeneration, focal adhesion, actin cytoskeleton, proteasome, cell cycle, DNA replication, and oxidative phosphorylation. Finally, we revealed genes and pathways (referring to cancer, Huntington’s disease, MAPK signalling, focal adhesion, actin cytoskeleton, oxidative phosphorylation, and metabolic signalling) that are coregulated during cellular senescence andin vivotissue ageing. The molecular commonalities between cellular senescence and tissue ageing are also highlighted by the fact that pathways that were overrepresented exclusively in the biopsy- or cell-based datasets are modules either of the same reference pathway (e.g., metabolism) or of closely interrelated pathways (e.g., thyroid cancer and melanoma). Our reported meta-analysis has revealed novel age-related genes, setting thus the basis for more detailed future functional studies.

scholarly journals Interaction between transcriptional activator protein LAC9 and negative regulatory protein GAL80.

1989 ◽  
Vol 9 (7) ◽  
pp. 2950-2956 ◽  
Author(s):  
J M Salmeron ◽  
S D Langdon ◽  
S A Johnston
Keyword(s):  
Transcriptional Activation ◽  
Kluyveromyces Lactis ◽  
Regulatory Protein ◽  
Wild Type ◽  
Galactose Metabolism ◽  
Metabolism Regulation ◽  
Transcriptional Activator Protein ◽  
The Difference ◽  
Carboxy Terminal

In Saccharomyces cerevisiae, transcriptional activation mediated by the GAL4 regulatory protein is repressed in the absence of galactose by the binding of the GAL80 protein, an interaction that requires the carboxy-terminal 28 amino acids of GAL4. The homolog of GAL4 from Kluyveromyces lactis, LAC9, activates transcription in S. cerevisiae and is highly similar to GAL4 in its carboxyl terminus but is not repressed by wild-type levels of GAL80 protein. Here we show that GAL80 does repress LAC9-activated transcription in S. cerevisiae if overproduced. We sought to determine the molecular basis for the difference in the responses of the LAC9 and GAL4 proteins to GAL80. Our results indicate that this difference is due primarily to the fact that under wild-type conditions, the level of LAC9 protein in S. cerevisiae is much higher than that of GAL4, which suggests that LAC9 escapes GAL80-mediated repression by titration of GAL80 protein in vivo. The difference in response to GAL80 is not due to amino acid sequence differences between the LAC9 and GAL4 carboxyl termini. We discuss the implications of these results for the mechanism of galactose metabolism regulation in S. cerevisiae and K. lactis.

scholarly journals mTORC1 controls phase-separation and the biophysical properties of the cytoplasm by tuning crowding

2017 ◽  
Author(s):  
M. Delarue ◽  
G.P. Brittingham ◽  
S. Pfeffer ◽  
I.V. Surovtsev ◽  
S. Ping-lay ◽  
...  
Keyword(s):  
Phase Separation ◽  
Fluorescent Protein ◽  
Effective Diffusion ◽  
Reaction Rates ◽  
Biophysical Properties ◽  
Cell Interior ◽  
Profound Impact ◽  
Mtorc1 Pathway

Summary (Abstract)Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed Genetically Encoded Multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein. GEMs self-assemble into bright, stable fluorescent particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can tune the effective diffusion coefficient of macromolecules ≥15 nm in diameter more than 2-fold without any discernable effect on the motion of molecules ≥5 nm. These mTORCI-dependent changes in crowding and rheology affect phase-separation both in vitro and in vivo. Together, these results establish a role for mTORCI in controlling both the biophysical properties of the cytoplasm and the phase-separation of biopolymers.

scholarly journals BIOLOGICALLY ACTIVE PEPTIDES IN METABOLISM REGULATION. PEPTONS, PEPTIDES, AMINO ACIDS, FATTY ACIDS, LIPOPROTEINS, LIPIDS, AND THE EFFECT OF NUTRICEUTICALS

2019 ◽  
Vol 64 (1) ◽  
pp. 14-23 ◽  
Author(s):  
A. V. Aripovsky ◽  
V. N. Titov
Keyword(s):  
Homo Sapiens ◽  
Close Association ◽  
Biologically Active ◽  
Functional Difference ◽  
Small Molecular Weight ◽  
Active Peptides ◽  
Metabolism Regulation ◽  
General Pathology ◽  
Biologically Active Peptides

According to phylogenetic theory of general pathology, formation of multicellular organisms started when each cell (a unicellular organism) reached the first level of relative biological perfection. By that time the stimuli for perfection of the unicellular exhausted, and formation of the multicellular became a biological necessity. All cells, being associated, formed the second level of relative biological perfection within the principle of biological succession. The association included highly organized unicellular organisms with their specific autocrine biological functions and reactions. At the second level of relative biological perfection all humoral mediators in paracrine regulated cell communities (PC) and organs were predominantly hydrophilic and short living. They had a small molecular weight and were probably biologically active peptides (BAP). We believe that functional difference of PC and later of organs is based on differentiation of lysosomal function and production of various enzymes involved in proteolysis of dietary proteins. This allowed various PC and organs to form chemically and functionally different BAP pools from one protein upon proteolysis. Individual peptide pools in PC created the basis for morphologically and functionally different cells and organs. Cell that produces peptides can modify their concentration, chemical parameters and ratios by varying the selectivity of its proteases. In vivo regulation of metabolism by BAP has a common root in bacteria, plants and vertebrates, including Homo sapiens. The third level of relative biological perfection in the organism has formed in close association with cognitive biological function.

scholarly journals Alternative pathways of zeaxanthin biosynthesis in a Flavobacterium species. Experiments with nicotine as inhibitor

1974 ◽  
Vol 144 (2) ◽  
pp. 231-243 ◽  
Author(s):  
J C B McDermott ◽  
D J Brown ◽  
G Britton ◽  
T W Goodwin
Keyword(s):  
Cyclization Reaction ◽  
Biosynthetic Pathways ◽  
Anaerobic Conditions ◽  
Anaerobic Process ◽  
Alternative Pathways ◽  
Nicotine Concentration ◽  
Β Carotene

In Flavobacterium R1519, nicotine blocks zeaxanthin biosynthesis by specifically inhibiting the cyclization reaction. Lycopene (at high nicotine concentrations, e.g. 7.5mm) and rubixanthin (at low nicotine concentration, e.g. 1mm) replace zeaxanthin as the main carotenoid. On removal of the nicotine lycopene is converted into β-carotene under anaerobic conditions and into zeaxanthin in the presence of O2. The conversion in vivo of β-carotene into zeaxanthin was also demonstrated. Cyclization (an anaerobic process) thus precedes hydroxylation (O2-requiring) in the biosynthesis of zeaxanthin. The conversion in vivo of rubixanthin into β-cryptoxanthin and into zeaxanthin was demonstrated, thus indicating the operation of alternative pathways of zeaxanthin biosynthesis. Several alternative biosynthetic pathways are considered and the results are also discussed in terms of reaction sequences of carotenoid ‘half-molecules’.

scholarly journals New Insights in (Poly)phenolic Compounds: From Dietary Sources to Health Evidence

Foods ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 543 ◽  
Author(s):  
Raúl Domínguez-Perles ◽  
Nieves Baenas ◽  
Cristina García-Viguera
Keyword(s):  
Plant Secondary Metabolites ◽  
Industrial Sector ◽  
In Vivo Models ◽  
Synthetic Drugs ◽  
Health And Nutrition ◽  
Points Of View ◽  
Joint Contribution ◽  
New Strategies

Nowadays, there is a gap between the theoretical bioactivity of (poly)phenols and their real influence in health, once ingested. Due to this, new studies, including in vitro and in vivo models that allow for exploring bioaccessibility, bioavailability, and bioactivity, need to be developed to understand the actual importance of consuming functional foods, rich in these plant secondary metabolites. Moreover, current new strategies need to be developed to enhance the content of these foods, as well as setting up new formulations rich in bioaccessible and bioavailable compounds. Altogether, it could give a new horizon in therapy, expanding the use of these natural functional compounds, ingredients, and foods in the clinical frame, reducing the use of synthetic drugs. As a result, the joint contribution of multidisciplinary experts from the food science, health, and nutrition areas, together with the industrial sector, would help to reach these objectives. Taking this into account, diverse studies have been included in this study, which comprises different strategies to approach these objectives from different, complementary, points of view, ranging from the enrichment of by-products in bioactive compounds, through different agricultural techniques, to the assimilation of these compounds by the human body, both in vitro and in vivo, as well as by clinical studies.

scholarly journals Molecular immunocytochemistry of the CuZn superoxide dismutase in rat hepatocytes.

1988 ◽  
Vol 107 (6) ◽  
pp. 2169-2179 ◽  
Author(s):  
L Y Chang ◽  
J W Slot ◽  
H J Geuze ◽  
J D Crapo
Keyword(s):  
Superoxide Dismutase ◽  
Rat Liver ◽  
Oxidant Stress ◽  
Rat Hepatocytes ◽  
Reaction Rates ◽  
Cytoplasmic Matrix ◽  
Cytosolic Proteins ◽  
Cuzn Superoxide Dismutase ◽  
O2 Production

The distribution of CuZn superoxide dismutase (SOD) molecules in subcellular organelles in rat liver hepatocytes was studied using integrated biochemical, stereological, and quantitative immunocytochemical techniques. A known concentration of purified CuZn SOD in 10% gelatin was embedded alongside the liver tissue for the calculation of CuZn SOD concentrations in hepatocyte organelles and total CuZn SOD in the rat liver. Most of the CuZn SOD was located in the cytoplasmic matrix (73.1%) and in the nucleus (11.9%) with concentrations of 1.36 and 0.71 mg/cm3, respectively. Lysosomes contained the highest concentration (5.81 mg/cm3). Only low concentrations were measured in mitochondria (0.21 mg/cm3). Membrane-bound spaces of rough endoplasmic reticulum (ER), smooth ER, and the Golgi system did not contain significant concentrations of the enzyme. By adding up the concentrations in all subcellular compartments, a total liver content of CuZn SOD was established from the immunocytochemical measurements (0.386 +/- 0.028 mg/gm liver) that agreed closely with those obtained by biochemical assays (0.380 +/- 0.058 mg/gm liver). The average distances between two CuZn SOD molecules can be calculated from enzyme concentrations. It was determined that CuZn SOD molecules in the cytoplasmic matrix and nucleus were 34 and 42 nm apart, respectively. In peroxisomes and mitochondria, average intermolecular distance increased to approximately 60 nm and increased to 136 nm in smooth ER. CuZn SOD is a relatively abundant protein in the cytosol of hepatocytes and its distribution overlaps with major sites of O2- production. The efficiency of protection CuZn SOD can provide to cytosolic proteins from attacks by superoxide anion depends on the rate of O2- production, distribution of CuZn SOD relative to cytosolic proteins, and the relative reaction rates between O2- with both cytosolic proteins and CuZn SOD. Future studies of these substrate-enzyme relationships in vivo can lead to a greater understanding of how cells handle oxidant stress.

scholarly journals Screening of Insecticidal Activity of Podophyllotoxin Analogues against Athetis dissimilis

2019 ◽  
Vol 14 (1) ◽  
pp. 1934578X1901400 ◽  
Author(s):  
Zhiping Che ◽  
Yuee Tian ◽  
Jinming Yang ◽  
Shengming Liu ◽  
Jia Jiang ◽  
...  
Keyword(s):  
Insecticidal Activity ◽  
Structural Modification ◽  
Plant Secondary Metabolites ◽  
Mortality Rates ◽  
Fourth Instar ◽  
Chemical Structures ◽  
Commercial Plant ◽  
Ongoing Work ◽  
Insecticidal Activities

As our ongoing work on research of natural-product-based insecticidal agents, eighteen podophyllotoxin analogues with diverse chemical structures were evaluated for their insecticidal activities against the pre-fourth-instar larvae of Athetis dissimilis Hampson in vivo at the concentration of 1 mg/mL. Among all the reported analogues, compounds 6, 8, 12, 13, 15 and 17 showed more potent insecticidal activities than matrine, quinine and toosendanin, three commercial plant secondary metabolites. 2′,6′-Dichloropodophyllotoxin (8) and 2′,6′-dichloroepipodophyllotoxin (13) exhibited the most pronounced and promising insecticidal activity with the final corrected mortality rates of greatly 60%. This suggested that variation of chemical structures in the podophyllotoxin skeleton conspicuously has effect on the insecticidal activity profiles of podophyllotoxin analogues. Moreover, SAR revealed that the substituents and configuration were critical for their insecticidal activities. The results may be useful in guiding further design and structural modification of podophyllotoxins in the development of potential novel insecticidal agents.

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