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Omics Technology: Novel Approach for Screening of Plant-Based Traditional Medicines
Published in Megh R. Goyal, Hafiz Ansar Rasul Suleria, Ademola Olabode Ayeleso, T. Jesse Joel, Sujogya Kumar Panda, The Therapeutic Properties of Medicinal Plants, 2019
Rojita Mishra, Satpal Singh Bisht, Mahendra Rana
Genomics plays an important role in the herbal drugs and their discovery. More specifically is the development of metagenomics and advance bioinformatics technology for gene mining, which can cluster the diversity of secondary metabolite pathway genes and correlation of these data for their biosynthetic pathways. Mainly if we know the genes and the networking of biosynthetic pathways, which is possible through genomics followed by gene mining with bioinformatics tools, then natural drug production can be channelized through metabolic engineering. Genes can be targeted for expression from inactive clusters, or the pathway can be modified for the production of more useful secondary metabolites.
Conversion of Natural Products from Renewable Resources in Pharmaceuticals by Cytochromes P450
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Giovanna Di Nardo, Gianfranco Gilardi
Flavonoids beneficial properties are well known and, also for these molecules, metabolic engineering is providing a powerful tool to produce them. For example, two of them, kaempferol and quercetin, that showed potent antioxidants and anti-obesity compounds (Griffiths et al., 2016), were produced by reconstructing the basic flavonoid pathway in Escherichia coli (Leonard et al., 2006; Leonard et al., 2007). In particular, the cytochrome P450 acting as a flavonoid 3′,5′-hydroxylase (F3′5′H from Catharanthus roseus) was fused with a P450-reductase and introduced in the bacterial strain (Leonard et al., 2006).
Ethnobotany Post-Genomic Horizons and Multidisciplinary Approaches for Herbal Medicine Exploration: An Overview
Published in T. Pullaiah, K. V. Krishnamurthy, Bir Bahadur, Ethnobotany of India, 2017
Manickam Tamil Selvi, Ankanagari Srinivas
In plants increased production of important metabolites is accomplished through genetic engineering. Metabolic engineering improves the metabolite composition at the cellular levels thereby eliminating the undesired effects and enhances the production of existing secondary metabolites in plants (Ramesh Kumar, 2016). Recent advances in metabolic engineering have allowed increase in the concentration of lead components and identifying non characterized pathways. For example, metabolic engineering was used to produce paclitaxel under in vitro conditions (Engel et al., 2008).
Improving protein glycan coupling technology (PGCT) for glycoconjugate vaccine production
Published in Expert Review of Vaccines, 2020
Jennifer Mhairi Dow, Marta Mauri, Timothy Alexander Scott, Brendan William Wren
Depletion of the Braun’s lipoprotein gene generated a so called ‘leaky’ E. coli strain capable of releasing glycoconjugates in the supernatant, reducing purification complexity [104,105]. The risk of endotoxin contamination in the end product can be reduced by engineering strains with detoxified lipid A (unpublished work). Metabolic screening and metabolic engineering efforts can be deployed to further optimize and enhance glycoconjugate production yield [106–108]. More recently, PGCT has been performed using host bacteria other than E. coli. Examples to date include the use of Salmonella enterica sv. Paratyphi A [59] and Yersinia enterocolitica O9, which acts as a surrogate for Brucella abortus and Brucella suis due to the similarity with Y. enterocolitica’s O9 glycan repeat unit [109,137]. However, this requires the host to be relatively genetically tractable. Greater knowledge of glycosylation in bacteria continuously feeds into the PGCT toolbox, and the library of tailor-made ‘glycostrains’ continues to grow.
A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis
Published in Pharmaceutical Biology, 2018
Zi-Long Wang, Shuang Wang, Yi Kuang, Zhi-Min Hu, Xue Qiao, Min Ye
Scutellaria baicalensis contains at least 126 small molecules and 6 polysaccharides. It possesses anti-tumor, anti-viral, anti-microbial, anti-inflammatory, antioxidative, and neuroprotective activities. Chemical compounds responsible for many of these activities are still unknown, though the bioactivities of a few major compounds (baicalin, baicalein, wogonoside, and wogonin) have been extensively studied. Recently, our group reported the comprehensive correlations of chemicals and bioactivities of another popular herbal medicine Gan-Cao (licorice, Glycyrrhiza uralensis Fisch), and discovered a number of promising bioactive natural products (Ji et al. 2016). Similar research strategy could be applied to Huang-Qin to discover potential new drugs. In fact, the clinical trial of wogonin as an anti-cancer drug candidate has recently been approved by the State Drug Administration of China. On the other hand, the identified major bioactive compounds could be used as chemical markers to improve quality control of Huang-Qin crude drugs and related patent drugs. Furthermore, biosynthetic studies could help large-scale production of the bioactive compounds by metabolic engineering. Although enzymes involved in the biosynthesis of free flavones have been reported for S. baicalensis, many post-modification enzymes have yet to be characterized, including those responsible for the hydroxylation, methylation, and glycosylation reactions.
Full-length recombinant antibodies from Escherichia coli: production, characterization, effector function (Fc) engineering, and clinical evaluation
Published in mAbs, 2022
In two reports published in 2020,79,80 Zhang et al. described a system-based synthetic biology approach using small regulatory RNAs to knock down gene expression in a modular fashion utilizing cetuximab as a target FL-IgG for the improvement of expression. In the first report, they took a systematic metabolic engineering approach, using three modules, glycolytic module 1, tricarboxylic acid cycle module 2, and amino acid biosynthesis module 3. They identified the pyruvate dehydrogenase (aceF) gene in module 1, citrate synthase (gltA) and aconitate hydratase A (acnA) genes in module 2, and phosphoserine phosphatase (serB) gene in module 3 as being beneficial. By combining all four mutations into a single strain with optimized fermentation conditions, they achieved a titer of ~5 mg/L in shake-flask and ~200 mg/L in high cell density fermentation.79 In the second report, a similar three-module approach (pyruvate metabolism in module 1, protease deletion in module 2, and chaperone coexpression in module 3), led to the identification of phosphate acetyltransferase (pta), acetyl-CoA synthetase (acs), and phosphoenolpyruvate synthetase (pps) genes in module 1, serine endoproteases degS and degQ genes in module 2, and disulfide oxidoreductase dsbA gene in module 3 as being beneficial for the expression of cetuximab. Combining all the genetic manipulations into a single strain (i.e., repression of pta, ppsA, degS, and degQ genes, and overexpression of acs and dsbA genes) with optimized inducer concentration resulted in a titer of 4 mg/L in shake-flask and ~150 mg/L in fed-batch culture.80 It is currently unknown whether the effects of combining all the beneficial modifications described in these two studies into a single strain would be additive or not.