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(Synthetic biology)

C Schirmer, J Posseckardt, A Kick, K Rebatschek, W Fichtner, K Ostermann, A Schuller, G Rödel, M Mertig
Recently it has been proposed to use sensors based on genetically engineered reporter cells to perform continuous online water monitoring. Here we describe the design, assembly and performance of a novel flow-through device with immobilized genetically modified yeast cells that produce a fluorescent protein upon stimulation with diclofenac whose intensity is then detected by fluorescence microscopy. Although other devices employing immobilized cells for the detection of various analytes have already been described before, as novelty our system allows safe enclosure of the sensor cells, and thus, to obtain fluorescent signals that are not falsified by a loss of cells...
August 12, 2018: Journal of Biotechnology
Xiang Zhou, Dongbao Yao, Miao He, Shiyan Xiao, HaoJun Liang
The synthetic DNA hybridization probe has proved its importance in biology and biotechnology. In this study, taking advantage of a novel analytical technique called dual polarization interferometry (DPI), the influence of the toehold strategy of on-chip DNA hybridization probe on the discrimination of single nucleotide polymorphism (SNP) was investigated. Through adjusting the toehold length, the toehold strategies of on-chip toehold exchange probe were thoroughly optimized. For the "6/5" probe, an optimal discrimination factor of 78% against the spurious target was achieved...
August 15, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Sanchita Bhadra, Arti Pothukuchy, Raghav Shroff, Austin W Cole, Michelle Byrom, Jared W Ellefson, Jimmy D Gollihar, Andrew D Ellington
We have found that the overproduction of enzymes in bacteria followed by their lyophilization leads to 'cellular reagents' that can be directly used to carry out numerous molecular biology reactions. We demonstrate the use of cellular reagents in a variety of molecular diagnostics, such as TaqMan qPCR with no diminution in sensitivity, and in synthetic biology cornerstones such as the Gibson assembly of DNA fragments, where new plasmids can be constructed solely based on adding cellular reagents. Cellular reagents have significantly reduced complexity and cost of production, storage and implementation, features that should facilitate accessibility and use in resource-poor conditions...
2018: PloS One
Xianwen Long, Yiming Ding, Jun Deng
The first total syntheses of cytochalasan dimers asperchalasines A, D, E and H have been accomplished. The key steps of the synthesis include a highly stereoselective intermolecular Diels-Alder reaction and a HWE macrocyclization to establish the key monomer aspochalasin B and an intermolecular Diels-Alder reaction followed by a biomimetic oxidative heterodimerization via 5+2 cycloaddition to furnish asperchalasine A. The synthetic efforts provide insight into the biosynthetic pathway of cytochalasan dimers and enables the further study of their biological properties...
August 15, 2018: Angewandte Chemie
Heber Gamboa-Melendez, Macarena Larroude, Young Kyoung Park, Pauline Trebul, Jean-Marc Nicaud, Rodrigo Ledesma-Amaro
Synthetic biology is an emergent field of research whose aim is to make biology an engineering discipline, thus permitting to design, control, and standardize biological processes. Synthetic biology is therefore expected to boost the development of biotechnological processes such as protein production and enzyme engineering, which can be significantly relevant for lipases and esterases.
2018: Methods in Molecular Biology
Francisco Valero
The production of heterologous lipases is one of the most promising strategies to increase the productivity of the bioprocesses and to reduce costs, with the final objective that more industrial lipase applications could be implemented.In this chapter, an overview of the new success in synthetic biology, with traditional molecular genetic techniques and bioprocess engineering in the last 5 years in the cell factory Pichia pastoris, the most promising host system for heterologous lipase production, is presented...
2018: Methods in Molecular Biology
Dalal Asker, Tarek S Awad, Teruhiko Beppu, Kenji Ueda
Zeaxanthin is a yellow xanthophyll, dihydroxy-carotenoid, that is naturally found in some of the green, orange, and yellow vegetables and fruits and has a powerful antioxidant activity. Epidemiological evidences suggest that increasing the consumption of zeaxanthin in the diet is associated with a lower risk of age-related macular degeneration (ARMD) and cataracts, two of the leading causes of blindness in the world. Zeaxanthin is a promising nutraceutical/colorant with many applications in feed, food, and pharmaceutical industries...
2018: Methods in Molecular Biology
Mariza Bortolanza, Glauce C Nascimento, Sergio B Socias, Diego Ploper, Rosana N Chehín, Rita Raisman-Vozari, Elaine Del-Bel
The prevalence of Parkinson's disease, which affects millions of people worldwide, is increasing due to the aging population. In addition to the classic motor symptoms caused by the death of dopaminergic neurons, Parkinson's disease encompasses a wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkinson's disease progression are being developed, drug repurposing, which is the use of existing drugs that have passed numerous toxicity and clinical safety tests for new indications, can be used to identify treatment compounds...
August 14, 2018: Journal of Neural Transmission
Alagesan Muthukumar, Subramani Sangeetha, Govindasamy Sekar
α-Keto amides are a key frame in biology, medicinal chemistry and synthetic chemistry as drug molecules and key intermediates. Based on the structural aspect, an acyclic α-keto amide has multiple reactive centres which have electrophilic and nucleophilic characters. In this review, we focus on the recent developments of both asymmetric and achiral reactions involving acyclic α-keto amides as the reactants for the synthesis of cyclic and acyclic molecules through the formation of C-C, C-O, C-N and C-H bonds...
August 15, 2018: Organic & Biomolecular Chemistry
Farida Tripodi, Federico Dapiaggi, Fulvia Orsini, Roberto Pagliarin, Guido Sello, Paola Coccetti
Several synthetic combretastatin A4 ( CA-4 ) derivatives were recently prepared to increase the drug efficacy and stability of the natural product isolated from the South African tree Combretum caffrum . A group of ten 3-amino-2-azetidinone derivatives, as combretastatin A4 analogues, was selected through docking experiments, synthesized and tested for their anti-proliferative activity against the colon cancer SW48 cell line. These molecules, through the formation of amide bonds in position 3, allow the synthesis of various derivatives that can modulate the activity with great resistance to hydrolytic conditions...
May 1, 2018: MedChemComm
Yasser Hussein Eissa Mohammed, Shaukath Ara Khanum
In modern biology, one of the major topics of importance is progress in anti-cancer drugs with specific targets. The angiopreventive and in vitro tumor inhibition activities of novel synthetic benzophenone analogs have been investigated intensively and explored in a very systematic way. Novel benzophenone analogs ( 9a-d and 10a-d ) substituted with methyl, chloro and fluoro groups at different positions on an identical chemical backbone and incorporating variations in the number of substituents have been synthesized in a multistep process and characterized...
April 1, 2018: MedChemComm
S McAuley, A Huynh, T L Czarny, E D Brown, J R Nodwell
Small molecule disruption of the bacterial membrane is both a challenge and interest for drug development. While some avoid membrane activity due to toxicity issues, others are interested in leveraging the effects for new treatments. Existing assays are available for measuring disruption of membrane potential or membrane permeability, two key characteristics of the bacterial membrane, however they are limited in their ability to distinguish between these properties. Here, we demonstrate a high throughput assay for detection and characterization of membrane active compounds...
March 1, 2018: MedChemComm
Fei Yang, Mingyan Zhu, Jinyi Zhang, Huchen Zhou
Boron-containing compounds which possess unique and attractive properties have received increasing attention from the pharmaceutical industry and academia recently. They have shown interesting and useful biological activities, including antibacterial, antifungal, antiparasitic, antiviral, and anti-inflammatory activities. In this review, the synthetic strategies for various boron-containing compounds, including peptidyl boronic acids, benzoxaboroles, benzoxaborines, benzodiazaborines, amine carboxyboranes, and amine cyanoboranes are summarized...
February 1, 2018: MedChemComm
Shiva Krishna Reddy Guduru, Prabhat Arya
Over the years, rapamycin has attracted serious attention due to its remarkable biological properties and as a potent inhibitor of the mammalian target of rapamycin (mTOR) protein through its binding with FKBP-12. Several efficient strategies that utilize synthetic and biosynthetic approaches have been utilized to develop small molecule rapamycin analogs or for synthesizing hybrid compounds containing a partial rapamycin structure to improve pharmacokinetic properties. Herein, we report selected case studies related to the synthesis of rapamycin-derived compounds and hybrid molecules to explore their biological properties...
January 1, 2018: MedChemComm
XiXi Xu, Tristan Rawling, Ariane Roseblade, Roger Bishop, Alison T Ung
Tricyclic alkaloid-like compounds were synthesised in a few steps, via the bridging Ritter reaction. The compounds were evaluated for their antiproliferative activity against the MCF-7 and the aggressive MDA-MB-231 breast cancer cells. The anti-cancer activities of 2c were found to be selective towards the aggressive and more challenging to treat triple negative (MDA-MB-231) cell line while exhibiting no antiproliferative activities towards the MCF-7 cells at the highest concentration tested (50 μM). The IC50 of compound 2c was determined to be 7...
November 1, 2017: MedChemComm
Michael Gapinske, Alan Luu, Jackson Winter, Wendy S Woods, Kurt A Kostan, Nikhil Shiva, Jun S Song, Pablo Perez-Pinera
CRISPR gene editing has revolutionized biomedicine and biotechnology by providing a simple means to engineer genes through targeted double-strand breaks in the genomic DNA of living cells. However, given the stochasticity of cellular DNA repair mechanisms and the potential for off-target mutations, technologies capable of introducing targeted changes with increased precision, such as single-base editors, are preferred. We present a versatile method termed CRISPR-SKIP that utilizes cytidine deaminase single-base editors to program exon skipping by mutating target DNA bases within splice acceptor sites...
August 15, 2018: Genome Biology
Zhijie Qin, Qiulin Yue, Yan Liang, Jingjing Zhang, Lin Zhou, Orlando Borrás Hidalgo, Xinli Liu
Quantum dots are important fluorescent semiconductor nano-crystals with distinguished electrical and optical properties and have gained great interest in many fields. The chemical and physical synthetic methods are usually not favorable for biological application due to high energy-consumption procedure and residual toxic chemicals. The development of novel "green" routes to prepare bio-compatible cadmium sulfide quantum dots constitutes a promising substituted approach. We used the white rot fungus Trametes versicolor for the biosynthesis of cadmium sulfide quantum dots taking account of the adsorption property of this fungus...
August 11, 2018: Journal of Biotechnology
Stanley Chun-Wei Lee, Khrystyna North, Eunhee Kim, Eunjung Jang, Esther Obeng, Sydney X Lu, Bo Liu, Daichi Inoue, Akihide Yoshimi, Michelle Ki, Mirae Yeo, Xiao Jing Zhang, Min Kyung Kim, Hana Cho, Young Rock Chung, Justin Taylor, Benjamin H Durham, Young Joon Kim, Alessandro Pastore, Sebastien Monette, James Palacino, Michael Seiler, Silvia Buonamici, Peter G Smith, Benjamin L Ebert, Robert K Bradley, Omar Abdel-Wahab
Mutations affecting RNA splicing factors are the most common genetic alterations in myelodysplastic syndrome (MDS) patients and occur in a mutually exclusive manner. The basis for the mutual exclusivity of these mutations and how they contribute to MDS is not well understood. Here we report that although different spliceosome gene mutations impart distinct effects on splicing, they are negatively selected for when co-expressed due to aberrant splicing and downregulation of regulators of hematopoietic stem cell survival and quiescence...
August 13, 2018: Cancer Cell
S Preethi Soundarya, A Haritha Menon, S Viji Chandran, N Selvamurugan
In the recent years, a paradigm shift is taking place where metallic/synthetic implants and tissue grafts are being replaced by tissue engineering approach. A well designed three-dimensional scaffold is one of the fundamental tools to guide tissue formation in vitro and in vivo. Bone is a highly dynamic and an integrative tissue, and thus enormous efforts have been invested in bone tissue engineering to design a highly porous scaffold which plays a critical role in guiding bone growth and regeneration. Numerous techniques have been developed to fabricate highly interconnected, porous scaffold for bone tissue engineering applications with the help of biomolecules such as chitosan, collagen, gelatin, silk, etc...
August 11, 2018: International Journal of Biological Macromolecules
Benjamin Des Soye, Samuel Davidson, Matthew Weinstock, Dan Gibson, Michael C Jewett
A new wave of interest in cell-free protein synthesis (CFPS) systems has shown their utility for producing proteins at high titers, establishing genetic regulatory element libraries (e.g., promoters, ribosome binding sites) in non-model organisms, optimizing biosynthetic pathways before implementation in cells, and sensing biomarkers for diagnostic applications. Unfortunately, most previous efforts have focused on a select few model systems, such as Escherichia coli. Broadening the spectrum of organisms used for CFPS promises to better mimic host cell processes in prototyping applications and open up new areas of research...
August 14, 2018: ACS Synthetic Biology
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