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Franken J.,Stellenbosch University | Burger A.,Stellenbosch University | Burger A.,Technology Innovation Agency | Swiegers J.H.,Stellenbosch University | Bauer F.F.,Stellenbosch University
Applied Microbiology and Biotechnology | Year: 2015

Industrial synthesis of l-carnitine is currently performed by whole-cell biotransformation of industrial waste products, mostly d-carnitine and cronobetaine, through specific bacterial species. No comparable system has been established using eukaryotic microorganisms, even though there is a significant and growing international demand for either the pure compound or carnitine-enriched consumables. In eukaryotes, including the fungus Neurospora crassa, l-carnitine is biosynthesized through a four-step metabolic conversion of trimethyllysine to l-carnitine. In contrast, the industrial yeast, Saccharomyces cerevisiae lacks the enzymes of the eukaryotic biosynthesis pathway and is unable to synthesize carnitine. This study describes the cloning of all four of the N. crassa carnitine biosynthesis genes and the reconstruction of the entire pathway in S. cerevisiae. The engineered yeast strains were able to catalyze the synthesis of l-carnitine, which was quantified using hydrophilic interaction liquid chromatography electrospray ionization mass spectrometry (HILIC-ESI-MS) analyses, from trimethyllysine. Furthermore, the yeast threonine aldolase Gly1p was shown to effectively catalyze the second step of the pathway, fulfilling the role of a serine hydroxymethyltransferase. The analyses also identified yeast enzymes that interact with the introduced pathway, including Can1p, which was identified as the yeast transporter for trimethyllysine, and the two yeast serine hydroxymethyltransferases, Shm1p and Shm2p. Together, this study opens the possibility of using an engineered, carnitine-producing yeast in various industrial applications while providing insight into possible future strategies aimed at tailoring the production capacity of such strains. © 2015, Springer-Verlag Berlin Heidelberg.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: INT-01-2015 | Award Amount: 999.95K | Year: 2016

The STI cooperation between the EU and South Africa as originally framed by the South Africa-EU Scientific and Technological Cooperation Agreement and as constantly steered by the JSTCC requires a support mechanism which can translate and facilitate policy decisions, and provide intelligence and information services to various actors and stakeholders. In previous years the ESASTAP project series (ESASTAP, ESASTAP-2 and ESASTAP\) has successfully provided this support to the bilateral dialogue. The proposed ESASTAP 2020 project is a coordination and support action that aims at advancing further the EU-SA bilateral STI cooperation, building on the work and results of three preceding actions and responding to the needs and recommendations at the policy dialogue level, in particular to the mandate of the JSTCC and to the adopted Roadmap for cooperation between South Africa and the European Union. The project aims to provide efficient services on three levels (priority areas): a. R&I Cooperation in areas of common interests (Horizon 2020 and others). b. Policy Dialogue between EU and SA and by increasing the knowledge of the EUs external environment. c. Provision of a Cooperation platform and tools to alleviate obstacles. These priority areas translate into four major objectives through which the project is aiming to address the specific challenges of the call.


Nwaka S.,World Health Organization | Ochem A.,World Health Organization | Besson D.,World Health Organization | Ramirez B.,World Health Organization | And 15 more authors.
BMC International Health and Human Rights | Year: 2012

A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and recognized by the African Network for Drugs and Diagnostics Innovation (ANDI), through a competitive criteria based process. The process identified a number of opportunities and challenges for health R&D and innovation in the continent: i) it provides a direct evidence for the existence of innovation capability that can be leveraged to fill specific gaps in the continent; ii) it revealed a research and financing pattern that is largely fragmented and uncoordinated, and iii) it highlights the most frequent funders of health research in the continent. The CoEs are envisioned as an innovative network of public and private institutions with a critical mass of expertise and resources to support projects and a variety of activities for capacity building and scientific exchange, including hosting fellows, trainees, scientists on sabbaticals and exchange with other African and non-African institutions. © 2012Nwaka et al.; licensee BioMed Central Ltd.


Traut-Johnstone T.,University of Johannesburg | Traut-Johnstone T.,Mintek | Kanyanda S.,University of the Western Cape | Kriel F.H.,Mintek | And 12 more authors.
Journal of Inorganic Biochemistry | Year: 2015

New heteroditopic, bi- and multidentate imino- and aminophosphine ligands were synthesised and complexed to [AuCl(THT)] (THT = tetrahydrothiophene). X-ray crystallography confirmed Schiff base formation in three products, the successful reduction of the imino-group to the sp3-hybridised amine in several instances, and confirmed the formation of mono-gold(I) imino- and aminophosphine complexes for four Au-complexes. Cytotoxicity studies in cancerous and non-cancerous cell lines showed a marked increase in cytotoxicity upon ligand complexation to gold(I). These findings were supported by results from the 60-cell line fingerprint screen of the Developmental Therapeutics Programme of the National Institutes of Health for two promising compounds. The cytotoxicity of some of these ligands and gold(I)complexes is due to the induction of apoptosis. The ligands and gold(I)complexes demonstrated selective toxicity towards specific cell lines, with Jurkat T cells being more sensitive to the cytotoxic effects of these compounds, while the non-cancerous human cell line KMST6 proved more resistant when compared to the cancerous cell lines. Results from the NIH DTP 60 cell-line fingerprint screen support the observed enhancement of cytotoxicity upon gold(I) complexation. One gold(I)complex induced high levels of apoptosis at concentrations of 50 μM in all the cell lines screened in this study, while some of the other compounds selectively induced apoptosis in the cell lines. These results point towards the potential for selective toxicity to cancerous cells through the induction of apoptosis. © 2015 Elsevier Inc. All rights reserved.


Dlamini Z.,Mangosuthu University of Technology | Ntlabati P.,Merck And Co. | Mbita Z.,University of Limpopo | Shoba-Zikhali L.,Technology Innovation Agency
Experimental and Molecular Pathology | Year: 2015

Pyruvate dehydrogenase kinase 4 (PDK4), a mammalian mitochondrial serine kinase has emerged as an interesting candidate for diabetes therapy. Due to the high prevalence of this disease especially type 2 diabetes (T2D) and the health complications associated with it, there is extensive effort to find the appropriate treatment. Understanding the regulation of PDK4 activity would therefore contribute significantly to the development of therapeutic agents. This research outlines the utilization of bioinformatics tools such as Interweaver, ClustalW and Protein Structure Visualizer, in order to predict proteins that potentially interact with PDK4 and possibly regulate its activity. Interweaver database identified 96 proteins that have possible interaction sites for PDK4. Protein p100/p49, containing a death domain that is known to have a role in suppressing apoptosis, was identified as a potential partner for PDK4. The alignment between p100/p49 primary sequence and that of PDK4 using ClustalW demonstrated sequence similarity between the two proteins. Swiss PDB Viewer then located the positions of the amino acids that are in the hypothetical protein binding motif of p100/p49 within the 3D structure of hPDK4. These amino acids were found to be located in the region of PDK4 which is known to bind protein substrates of PDK4 and may be accessible to other proteins as well. These findings were very interesting as PDK4 has not previously been associated with apoptosis and this could be the link between apoptosis and insulin resistance. Cell biology studies were then performed to verify the relationship between PDK4 and apoptosis. In this regard, HeLa and HepG2 cells were treated with apoptosis-inducing agents such as TNFα, C2-ceramide, and linoleic acid. These cells were then monitored for apoptosis and PDK4 mRNA expression using a DNA laddering assay as well as Real Time PCR. The results showed that these factors induced apoptosis in a concentration dependent manner and suppressed PDK4 mRNA levels. These findings suggested a relationship between PDK4 and apoptosis. © 2015.


PubMed | University of Limpopo, Technology Innovation Agency, Merck And Co. and Mangosuthu University of Technology
Type: Journal Article | Journal: Experimental and molecular pathology | Year: 2015

Pyruvate dehydrogenase kinase 4 (PDK4), a mammalian mitochondrial serine kinase has emerged as an interesting candidate for diabetes therapy. Due to the high prevalence of this disease especially type 2 diabetes (T2D) and the health complications associated with it, there is extensive effort to find the appropriate treatment. Understanding the regulation of PDK4 activity would therefore contribute significantly to the development of therapeutic agents. This research outlines the utilization of bioinformatics tools such as Interweaver, ClustalW and Protein Structure Visualizer, in order to predict proteins that potentially interact with PDK4 and possibly regulate its activity. Interweaver database identified 96 proteins that have possible interaction sites for PDK4. Protein p100/p49, containing a death domain that is known to have a role in suppressing apoptosis, was identified as a potential partner for PDK4. The alignment between p100/p49 primary sequence and that of PDK4 using ClustalW demonstrated sequence similarity between the two proteins. Swiss PDB Viewer then located the positions of the amino acids that are in the hypothetical protein binding motif of p100/p49 within the 3D structure of hPDK4. These amino acids were found to be located in the region of PDK4 which is known to bind protein substrates of PDK4 and may be accessible to other proteins as well. These findings were very interesting as PDK4 has not previously been associated with apoptosis and this could be the link between apoptosis and insulin resistance. Cell biology studies were then performed to verify the relationship between PDK4 and apoptosis. In this regard, HeLa and HepG2 cells were treated with apoptosis-inducing agents such as TNF, C2-ceramide, and linoleic acid. These cells were then monitored for apoptosis and PDK4 mRNA expression using a DNA laddering assay as well as Real Time PCR. The results showed that these factors induced apoptosis in a concentration dependent manner and suppressed PDK4 mRNA levels. These findings suggested a relationship between PDK4 and apoptosis.


Paquet T.,University of Cape Town | Gordon R.,Technology Innovation Agency | Waterson D.,ICC Inc | Witty M.J.,ICC Inc | Chibale K.,University of Cape Town
Future Medicinal Chemistry | Year: 2012

The current state of antimalarial drug resistance emphasizes the need for new therapies with novel modes of action that will add a significant benefit compared with current standards. In this regard, high throughput phenotypic whole-cell screening aids the discovery of novel antiplasmodial scaffolds that are inherently suited to hit-to-lead and lead-optimization efforts. The aminothiazoles and aminopyridines exemplify two such compound classes stemming from whole-cell screening. Respective structure-activity relationship determinations and subsequent optimization around these scaffolds led to frontrunner compounds in each series, which possess the desired antimalarial efficacy, bioavailability and metabolic stability to further progress medicinal chemistry programs. © 2012 Future Science Ltd.


Fayomi O.S.I.,Covenant University | Fayomi O.S.I.,Tshwane University of Technology | Fayomi O.S.I.,Technology Innovation Agency
Journal of Materials and Environmental Science | Year: 2015

Co-deposition of zinc metal matrix with ZnO composite was fabricated from electrolytic chloride based coating consisting of 20-40g/L ZnO particle. The resulting composite coatings were characterized using high optic microscope (OPM). The corrosion resistance properties of Zn-ZnO composite coatings were measure using linear polarization in 3.5% NaCl solution. The variation of amount of ZnO %wt. inclusion of the composite on micro-hardness was investigated using dura scan diamond base micro-hardness tester. The results obtained indicate that the introduction of ZnO particles in the deposition bath obviously increase significantly the hardness properties. The increases in hardness value are attributed to the realization of coherent and even precipitate into the metal lattice. The corrosion polarization resistance also improved slightly as against the MS. It was found that addition of ZnO %wt support strengthening characteristics toward hardness improvement with slight enhancement in anti-corrosion properties.


Fayomi O.S.I.,Covenant University | Fayomi O.S.I.,Tshwane University of Technology | Fayomi O.S.I.,Technology Innovation Agency | Loto C.A.,Covenant University | And 3 more authors.
International Journal of Electrochemical Science | Year: 2014

Zn-Al2O3 composite coating electrodeposits have been produced from chloride bath in the presence of Triethanolamine (TEA) and Monoethanolamine (MEA). The plating effect of TEA and MEA as addition agent on the Zn-Al2O3 alloy is investigated using SEM/EDS, x-ray diffraction (XRD) and atomic force microscope (AFM). The mechanical properties were examined through micro-hardness tester. The presence of TEA and MEA as a surface-active additive is also felt to accompany the performance of the fabricated coating. The SEM results for Zn-Al2O3 deposits in the presence of TEA/MEA indicate that surface-active additive have a strong influence on the deposit surface morphology and improved micro-hardness behavior which is assisted by the change in the deposition process parameter. © 2014 The Authors.

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