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Tania Michelle Roberts, Fabian Rudolf, Andreas Meyer, Rene Pellaux, Ellis Whitehead, Sven Panke, Martin Held
This corrects the article DOI: 10.1038/srep28166.
May 17, 2018: Scientific Reports
Tilmann Kuenzl, Xiaochun Li-Blatter, Puneet Srivastava, Piet Herdewijn, Timothy Sharpe, Sven Panke
The import of non-natural molecules is a recurring problem in fundamental as well as applied aspects of microbiology. Escherichia coli's dipeptide permease (Dpp) is an ABC-type multicomponent transporter system located in the cytoplasmic membrane, which is capable of transporting a wide range of di- and tripeptides with structurally and chemically diverse amino acid side chains into the cell. Given this low degree of specificity, Dpp was previously used as an entry gate to deliver natural and non-natural cargo molecules into the cell by attaching them to amino acid side chains of peptides, in particular the γ-carboxyl group of glutamate residues...
May 4, 2018: Applied and Environmental Microbiology
Panke Qu, Wei Zhang, Dapeng Li, Chao Zhang, Qingwei Liu, Xueyang Zhang, Xuesong Wang, Wenlong Dai, Yongfen Xu, Qibin Leng, Jin Zhong, Xia Jin, Zhong Huang
Infection with Zika virus (ZIKV) may lead to severe neurologic disorders. It is of significant importance and urgency to develop safe and effective vaccines to prevent ZIKV infection. Here we report the development of ZIKV subunit vaccines based on insect cell-produced recombinant proteins. The N-terminal approximately 80% region (designated as E80) and the domain III (designated as EDIII) of ZIKV envelope (E) protein were efficiently produced as secreted proteins in a Drosophila S2 cell expression system. Both E80 and EDIII could inhibit ZIKV infection in vitro, suggesting that they may have folded properly to display native conformations...
April 14, 2018: Antiviral Research
Mohammad Rohani, Saeed Razmeh, Gholam Ali Shahidi, Elham Alizadeh, Maryam Orooji
Pantothenate kinase-associated neurodegeneration (PKAN) is the most common form of neurodegeneration with brain iron accumulation, it is an autosomal recessive disease due to mutation in PANK 2 on chromosome 20, which causes the accumulation of iron in basal ganglia and production of free radicals that cause degeneration of the cells. Deferiprone is an iron chelator that was used in treatment of thalassemia patients, it can cross the blood-brain barrier and reverse the iron deposition in the brain. Five patients with genetically confirmed PKAN received 15 mg/kg deferiprone twice daily...
December 11, 2017: Neurology International
Erick T Tjhin, Christina Spry, Alan L Sewell, Annabelle Hoegl, Leanne Barnard, Anna E Sexton, Ghizal Siddiqui, Vanessa M Howieson, Alexander G Maier, Darren J Creek, Erick Strauss, Rodolfo Marquez, Karine Auclair, Kevin J Saliba
The malaria-causing blood stage of Plasmodium falciparum requires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the parasite by targeting CoA biosynthesis/utilisation. Their mechanism of action, however, remains unknown. Here, we show that parasites pressured with pantothenol or CJ-15,801 become resistant to these analogues...
April 2018: PLoS Pathogens
Arif Nurkanto, Ghulam Jeelani, Takehiro Yamamoto, Yoshiko Naito, Takako Hishiki, Mihoko Mori, Makoto Suematsu, Kazuro Shiomi, Tetsuo Hashimoto, Tomoyoshi Nozaki
The Coenzyme A (CoA), as a cofactor involved in >100 metabolic reactions, is essential to the basic biochemistry of life. Here, we investigated the CoA biosynthetic pathway of Entamoeba histolytica (E. histolytica), an enteric protozoan parasite responsible for human amebiasis. We identified four key enzymes involved in the CoA pathway: pantothenate kinase (PanK, EC, bifunctional phosphopantothenate-cysteine ligase/decarboxylase (PPCS-PPCDC), phosphopantetheine adenylyltransferase (PPAT) and dephospho-CoA kinase (DPCK)...
April 2018: International Journal for Parasitology, Drugs and Drug Resistance
Laurent R Chiarelli, Giorgia Mori, Beatrice Silvia Orena, Marta Esposito, Thomas Lane, Ana Luisa de Jesus Lopes Ribeiro, Giulia Degiacomi, Júlia Zemanová, Sára Szádocka, Stanislav Huszár, Zuzana Palčeková, Marcello Manfredi, Fabio Gosetti, Joël Lelièvre, Lluis Ballell, Elena Kazakova, Vadim Makarov, Emilio Marengo, Katarina Mikusova, Stewart T Cole, Giovanna Riccardi, Sean Ekins, Maria Rosalia Pasca
Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new antitubercular drugs as well as novel targets are crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and 7904688, which target the CTP synthetase PyrG, were identified and characterized. In this work, microbiological, biochemical, and in silico methodologies were used to demonstrate that both prodrugs possess a second target, the pantothenate kinase PanK...
February 16, 2018: Scientific Reports
Steven Schmitt, Marcel Walser, Michael Rehmann, Sabine Oesterle, Sven Panke, Martin Held
The ability of whole cells to catalyse multistep reactions, often yielding synthetically demanding compounds later used by industrial biotech or pharma, makes them an indispensable tool of synthetic chemistry. The complex reaction network employed by cellular catalysts and the still only moderate predictive power of modelling approaches leaves this tool challenging to engineer. Frequently, large libraries of semi-rationally generated variants are sampled in high-throughput mode in order to then identify improved catalysts...
February 14, 2018: Scientific Reports
Christine L Mac Donald, Jason Barber, Jason Wright, David Coppel, Nina De Lacy, Steve Ottinger, Suzanne Peck, Chris Panks, Kody Zalewski, Samantha Sun, Nancy Temkin
OBJECTIVE: Prior work suggests that younger athletes may be more vulnerable to postconcussive syndrome. We investigated measures of clinical outcome and quantitative volumetric imaging in 10- to 14-year-old adolescent athletes to better understand the impact of concussion on this younger population. SETTING: Outpatient clinics. PARTICIPANTS: Ten- to 14-year-old symptomatic pediatric sports concussion patients and typically developing active controls...
January 30, 2018: Journal of Head Trauma Rehabilitation
Leanne Barnard, Konrad J Mostert, Willem A L van Otterlo, Erick Strauss
Pantothenamides (PanAms) are analogues of pantothenate, the biosynthetic precursor of coenzyme A (CoA), and show potent antimicrobial activity against several bacteria and the malaria parasite in vitro. However, pantetheinase enzymes that normally degrade pantetheine in human serum also act on the PanAms, thereby reducing their potency. In this study, we designed analogues of the known antibacterial PanAm N-heptylpantothenamide (N7-Pan) to be resistant to pantetheinase by using three complementary structural modification strategies...
January 23, 2018: ACS Infectious Diseases
Xin Huang, Yongqi Chen, Shan Zhen, Lijuan Song, Mingqi Gao, Panke Zhang, Heng Li, Bingxin Yuan, Guanyu Yang
Organosulfides have great significance and value in synthetic and biological chemistry. To establish a versatile and green methodology for C-S bond generation, we successfully developed a new aerobic cross-dehydrogenative coupling of C-H and S-H to synthesize aryl sulfides in water, utilizing CoPcS as the catalyst and O2 as the oxidant. This protocol shows great tolerance of a wide range of substrates. A large variety of organosulfur compounds were produced in modest to excellent yields.
January 24, 2018: Journal of Organic Chemistry
Pei Xu, Xiaoli Chen, Panke Su
BACKGROUND: Long non-coding RNAs (lncRNAs) have been highlighted as promising biomarkers for several types of malignancies. The current meta-analysis sought to investigate the clinical value of lncRNA-based molecular signatures as biomarkers for diagnosis, subtype classification, and prognosis in diffuse large B cell lymphoma (DLBCL). METHODS: A systematic search of the online databases was carried out and data were retrieved by pairs of independent reviewers. Effect sizes of the diagnostic parameters were combined using a quantitative meta-analysis...
November 1, 2017: Clinical Laboratory
Krishna Sapkota, Faqing Huang
Dephospho coenzyme A (depCoA) is the last intermediate for CoA biosynthesis, and it can be used as a transcription initiator to prepare CoA-linked RNA by in vitro transcription. However, commercially available depCoA is expensive. We hereby describe a simple and efficient enzymatic synthesis of depCoA in a single-step from commercially available and inexpensive oxidized pantethine (Ox-Pan) and ATP. A plasmid (pCoaDAa) was constructed to co-express and co-purify two enzymes pantothenate kinase (PanK/coaA) and phosphopantetheine adenylyltransferase (PPAT/coaD)...
February 2018: Bioorganic Chemistry
Markus Jeschek, Sven Panke, Thomas R Ward
Residing at the interface of chemistry and biotechnology, artificial metalloenzymes (ArMs) offer an attractive technology to combine the versatile reaction repertoire of transition metal catalysts with the exquisite catalytic features of enzymes. While earlier efforts in this field predominantly comprised studies in well-defined test-tube environments, a trend towards exploiting ArMs in more complex environments has recently emerged. Integration of these artificial biocatalysts in enzymatic cascades and using them in whole-cell biotransformations and in vivo opens up entirely novel prospects for both preparative chemistry and synthetic biology...
January 2018: Trends in Biotechnology
Sabine Oesterle, Irene Wuethrich, Sven Panke
Prokaryotes modified stably on the genome are of great importance for production of fine and commodity chemicals. Traditional methods for genome engineering have long suffered from imprecision and low efficiencies, making construction of suitable high-producer strains laborious. Here, we review the recent advances in discovery and refinement of molecular precision engineering tools for genome-based metabolic engineering in bacteria for chemical production, with focus on the λ-Red recombineering and the clustered regularly interspaced short palindromic repeats/Cas9 nuclease systems...
2017: Advances in Applied Microbiology
Stephanie Karmann, Sven Panke, Manfred Zinn
Poly(hydroxyalkanoates) (PHAs) are bacterial polyesters offering a biodegradable alternative to petrochemical plastics. The intracellular formation and degradation of PHAs is a dynamic process that strongly depends on the availability of carbon and other nutrients. Carbon excess and nitrogen limitation are considered to favor PHA accumulation, whereas carbon limitation triggers PHA depolymerization when all other essential nutrients are present in excess. We studied the population dynamics of Pseudomonas putida KT2440 at the single cell level during different physiological conditions, favoring first PHA polymerization during growth on octanoic acid, and then PHA depolymerization during carbon limitation...
June 19, 2017: Bioengineering
Sabine Oesterle, Daniel Gerngross, Steven Schmitt, Tania Michelle Roberts, Sven Panke
Multiplexed gene expression optimization via modulation of gene translation efficiency through ribosome binding site (RBS) engineering is a valuable approach for optimizing artificial properties in bacteria, ranging from genetic circuits to production pathways. Established algorithms design smart RBS-libraries based on a single partially-degenerate sequence that efficiently samples the entire space of translation initiation rates. However, the sequence space that is accessible when integrating the library by CRISPR/Cas9-based genome editing is severely restricted by DNA mismatch repair (MMR) systems...
September 26, 2017: Scientific Reports
Markus Jeschek, Daniel Gerngross, Sven Panke
Elimination of metabolic flux imbalances in microbial cell factories is an important part in the establishment of viable biotechnological production processes. However, due to the high complexity of cellular metabolism, the limited a priori knowledge about the majority of production pathways and a lack of forward design standards, metabolic engineers strongly rely on empirical screening methodologies to achieve the required improvement of cell behavior. Combinatorial pathway engineering provides an interesting tool to identify global solutions for intricate pathways, but methods for the reduction of combinatorial library size are inevitably required to restrict the experimental effort to an affordable size...
October 2017: Current Opinion in Biotechnology
Rikke Søgaard Tolstrup, Marie Thue Pank, Lotte Sander, Torben Dørflinger
OBJECTIVE: Ureteropelvic junction obstruction (UPJO) is a common cause of symptomatic ureteral obstruction. The aim of this study is to assess the outcome of laparoscopic pyeloplasty in patients with UPJO. PATIENTS AND METHODS: Medical reports of 47 UPJO patients treated with laparoscopic pyeloplasty were retrospectively analysed. All patients were recruited from our center in the period 2004-2011. RESULTS: We evaluated 47 patients. Mean age was 36 years and mean hospital stay 3...
2017: BioMed Research International
Robert J Hart, Amanah Abraham, Ahmed S I Aly
Coenzyme A (CoA) is an essential universal cofactor for all prokaryotic and eukaryotic cells. In nearly all non-photosynthetic cells, CoA biosynthesis depends on the uptake and phosphorylation of vitamin B5 (pantothenic acid or pantothenate). Recently, putative pantothenate transporter (PAT) and pantothenate kinases (PanKs) were functionally characterized in P. yoelii . PAT and PanKs were shown to be dispensable for blood stage development, but they were essential for mosquito stages development. Yet, little is known about the cellular functions of the other enzymes of the CoA biosynthesis pathway in malaria parasite life cycle stages...
2017: Frontiers in Cellular and Infection Microbiology
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