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Emmanuelle Schmitt, Gabrielle Bourgeois, Muriel Gondry, Alexey Aleksandrov
Cyclodipeptide synthases (CDPSs) form various cyclodipeptides from two aminoacyl tRNAs via a stepwise mechanism with the formation of a dipeptidyl enzyme intermediate. As a final step of the catalytic reaction, the dipeptidyl group undergoes intramolecular cyclization to generate the target cyclodipeptide product. In this work, we investigated the cyclization reaction in the cyclodipeptide synthase AlbC using QM/MM methods and free energy simulations. The results indicate that the catalytic Y202 residue is in its neutral protonated form, and thus, is not likely to serve as a general base during the reaction...
May 4, 2018: Scientific Reports
Dong Wang, Yangyang Zhan, Dongbo Cai, Xiaoyun Li, Qin Wang, Shouwen Chen
The cyclodipeptide pulcherriminic acid synthesized by Bacillus licheniformis is an iron chelator and antagonizes certain pathogens by removing iron from the environment. But as the insoluble Fe-pulcherriminic acid complex cannot act as an iron carrier like siderophores, so excessive synthesized pulcherriminic acid causes iron starvation for the producer cells. At present, regulation of pulcherriminic acid synthesis and the mechanism by which B. licheniformis strikes a balance between biocontrol and self-protection from excessive iron removal remain unclear...
April 27, 2018: Applied and Environmental Microbiology
P J Jongen
Doctors and patients are increasingly choosing treatment options by means of the shared decision-making process. However, human decisions are subject to cognitive bias, i.e. systematic and predictable errors in probability estimation and information synthesis. Decision-making may also be hampered by incomplete information. Clinical Drug Profiles (CDPs) aim to provide up-to-date, evidence-based and independent information about drug characteristics that are relevant to doctors and patients alike in the context of shared decision-making...
2018: Nederlands Tijdschrift Voor Geneeskunde
Bingxin Fang, Jiaqi Shi, Li Qin, Mingbao Feng, Danru Cheng, Tantan Wang, Xuesheng Zhang
Polychlorinated diphenyl sulfides and polychlorinated diphenyl ethers are two types of dioxin-like pollutants, which are prevalent in aquatic environments. However, to date, limited information is available regarding their toxicity to green algae. In this study, growth inhibition, effect on pigment content, and oxidative stress potentials of 4,4'-di-CDPS and 4,4'-di-CDE on green algae Scenedesmus obliquus were investigated. The results indicate that the EC50 values of 4,4'-di-CDPS after 24, 48, 72, and 96 h of exposure were 1...
March 24, 2018: Environmental Science and Pollution Research International
Jing Liu, Huili Yu, Shu-Ming Li
Cyclodipeptide synthases (CDPSs) comprise normally 200-300 amino acid residues and are mainly found in bacteria. They hijack aminoacyl-tRNAs from the ribosomal machinery for cyclodipeptide formation. In this study, nine new CDPS genes from eight Streptomyces strains were cloned into pET28a vector and expressed in Escherichia coli. Structural elucidation of the isolated products led to the identification of one cyclo-L-Trp-L-Leu, two cyclo-L-Trp-L-Pro, and three cyclo-L-Trp-L-Trp synthases. Other three CDPSs produce cyclo-L-Trp-L-Ala or cyclo-L-Trp-L-Tyr as the major cyclodipeptide...
March 24, 2018: Applied Microbiology and Biotechnology
Simon Boecker, Stefan Grätz, Dennis Kerwat, Lutz Adam, David Schirmer, Lennart Richter, Tabea Schütze, Daniel Petras, Roderich D Süssmuth, Vera Meyer
Background: Fungal cyclodepsipeptides (CDPs) are non-ribosomally synthesized peptides produced by a variety of filamentous fungi and are of interest to the pharmaceutical industry due to their anticancer, antimicrobial and anthelmintic bioactivities. However, both chemical synthesis and isolation of CDPs from their natural producers are limited due to high costs and comparatively low yields. These challenges might be overcome by heterologous expression of the respective CDP-synthesizing genes in a suitable fungal host...
2018: Fungal Biology and Biotechnology
Muriel Gondry, Isabelle B Jacques, Robert Thai, Morgan Babin, Nicolas Canu, Jérôme Seguin, Pascal Belin, Jean-Luc Pernodet, Mireille Moutiez
Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated as aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS in 2002, the number of putative CDPSs in databases has increased exponentially, reaching around 800 in June 2017. They are likely to be involved in numerous biosynthetic pathways but the diversity of their products is still under-explored. Here, we describe the activity of 32 new CDPSs, bringing the number of experimentally characterized CDPSs to about 100...
2018: Frontiers in Microbiology
Leon Maser, Jan Herritsch, Robert Langer
The reactivity patterns of carbodiphosphoranes (CDPs) as ligands are much less explored than those of isoelectronic analogues. In the current manuscript, we investigate the reactivity of the carbodiphosphorane-based PCP nickel(ii) pincer complex [({dppm}2 C)NiCl]Cl (1) towards acids and bases, calculate proton affinities, analyse the bonding situation and tautomeric forms with the aim to evaluate whether CDPs can potentially act as cooperative ligands in catalysis (dppm = 1,1-bis(diphenylphosphino)methane)...
February 22, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Xiaohan Wang, Xiao Gong, Peng Li, Daowan Lai, Ligang Zhou
Cyclic depsipeptides (CDPs) are cyclopeptides in which amide groups are replaced by corresponding lactone bonds due to the presence of a hydroxylated carboxylic acid in the peptide structure. These peptides sometimes display additional chemical modifications, including unusual amino acid residues in their structures. This review highlights the occurrence, structures and biological activities of the fungal CDPs reported until October 2017. About 352 fungal CDPs belonging to the groups of cyclic tri-, tetra-, penta-, hexa-, hepta-, octa-, nona-, deca-, and tridecadepsipeptides have been isolated from fungi...
January 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Enrique Martínez-Carranza, Gabriel Y Ponce-Soto, Alma L Díaz-Pérez, Erasmo Cadenas, Valeria Souza, Jesús Campos-García
The Cuatro Ciénegas Basin (CCB) within the Chihuahuan Desert in México is an extremely oligotrophic oasis with negligible phosphorous levels, described as a hot spot of biodiversity, not only in stromatolites and microbial mats, but also in living forms in general. The microorganisms possess the capability to produce a wide variety of virulence factors, antibiotics, and quorum-sensing (QS) crosstalk signals such as non-ribosomal cyclodipeptides (CDPs) which enables them to colonize diverse ecological niches...
January 2018: Extremophiles: Life Under Extreme Conditions
Nobuyuki Onai, Jumpei Asano, Rumiko Kurosaki, Shoko Kuroda, Toshiaki Ohteki
The basic helix-loop-helix transcription factor E2-2 is essential for the development of plasmacytoid dendritic cells (pDCs) but not conventional DCs (cDCs). Here, we generated E2-2 reporter mice and demonstrated that an E2-2high fraction among common DC progenitors, which are a major source of pDCs and cDCs in the steady state, strictly gave rise to pDCs in the presence of Flt3 (Fms-like tyrosine kinase receptor-3) ligand ex vivo or in the secondary lymphoid organs when transferred in vivo. However, in the small intestine, some of these E2-2high progenitors differentiated into cDCs that produced retinoic acid...
December 18, 2017: International Immunology
Awdhesh Kumar Mishra, Jaehyuk Choi, Seong-Jin Choi, Kwang-Hyun Baek
Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters...
October 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kirsten Brockmeyer, Shu-Ming Li
Expression of a cyclodipeptide synthase gene from Nocardiopsis prasina (CDPS-Np) in Escherichia coli resulted in the formation of cyclo-(l-Tyr-l-Tyr) (1) as the minor and cyclo-(l-Tyr-l-Phe) (2) as the major products. Site-directed mutagenesis revealed a strong influence on product accumulation of the amino acid residues in pocket P1. An 8-fold increase in product formation for 1 and 10-fold for 2 were detected in the double mutant T82V_Y196F compared with the wild type.
November 22, 2017: Journal of Natural Products
Jerry Nedelman, Roland Fisch, Ke Hu, Ines Paule, Jocelyn Zhou
BACKGROUND AND OBJECTIVE: Pasireotide (SOM230, Signifor® ) is a somatostatin analog approved in a subcutaneous formulation for the treatment of Cushing's disease. This analysis characterizes the population pharmacokinetics (PopPK) of subcutaneous pasireotide jointly in healthy volunteers (HVs) and Cushing's disease patients (CDPs), evaluating the effects of age, body size, and population on pasireotide pharmacokinetics. METHODS: The analysis dataset included five phase I studies and one each from phase II and phase III...
October 14, 2017: Clinical Pharmacokinetics
Zhanghui Wang, Peibin Zhang, Fan Hu, Yifan Zhao, Liping Zhu
Organic micropollutants in aquatic environment such as plasticizer, pesticide and pharmaceuticals, have posed a serious threat to human health and are emerging as a great challenge to humanity. Traditional water treatment techniques fail to achieve high removal efficiency for low concentration of organic micropollutants. Here we demonstrate a water-insoluble crosslinked β-cyclodextrin (β-CD) polymer able to remove a broad-spectrum of organic micropollutants from water by rapid adsorption. A family of β-CD polymers (β-CDPs) were synthesized by nucleophilic aromatic substitution of β-CD hydroxyl groups and 4,4'-difluorodiphenylsulfone...
December 1, 2017: Carbohydrate Polymers
Lawrence Paszat, Rinku Sutradhar, Mary Ann O'Brien, Aisha Lofters, Andrew Pinto, Peter Selby, Nancy Baxter, Peter D Donnelly, Regina Elliott, Richard H Glazier, Robert Kyle, Donna Manca, Mary-Anne Pietrusiak, Linda Rabeneck, Nicolette Sopcak, Jill Tinmouth, Becky Wall, Eva Grunfeld
BACKGROUND: The Building on Existing Tools to Improve Chronic Disease Prevention and Screening (BETTER) cluster randomized trial in primary care settings demonstrated a 30% improvement in adherence to evidence-based Chronic Disease Prevention and Screening (CDPS) activities. CDPS activities included healthy activities, lifestyle modifications, and screening tests. We present a protocol for the adaptation of BETTER to a public health setting, and testing the adaptation in a cluster randomized trial (BETTER HEALTH: Durham) among low income neighbourhoods in Durham Region, Ontario (Canada)...
September 29, 2017: BMC Public Health
Shivaprasad Manchineella, N Arul Murugan, Thimmaiah Govindaraju
Ambidextrous supergelators are developed through structure-gelation screening of rationally designed cyclic dipeptides (CDPs). The organo- and hydrogels of CDPs were thoroughly characterized by their minimal gelation concentration (MGC) for organic and aqueous solvents, thermal stability (Tg), and viscoelastic properties. Intermolecular hydrogen bonding, the major driving force for gelation was evaluated using temperature-dependent nuclear magnetic resonance (NMR) spectroscopy. The contribution of attractive van der Waals interaction of tBoc group in driving CDP gelation was ascertained using β-cyclodextrin (β-CD)-adamantane carboxylic acid (AC)-based host-guest gelation and (1)H NMR studies...
September 14, 2017: Biomacromolecules
Donyez Frikha Dammak, Ziad Zarai, Soumaya Najah, Rayed Abdennabi, Lassaad Belbahri, Mostafa E Rateb, Hafedh Mejdoub, Sami Maalej
This study has focused on the isolation of twenty-three halophilic actinomycetes from two ponds of different salinity and the evaluation of their ability to exert an antimicrobial activity against both their competitors and several other pathogens. From the 23 isolates, 18 strains showed antagonistic activity, while 19 showed activities against one or more of the seven pathogen strains tested. Six strains exhibited consistent antibacterial activity against Gram-negative and Gram-positive pathogens characterized at the physiological and molecular levels...
2017: BioMed Research International
Seong Woo Noh, Rira Seo, Jung-Kwon Park, Md Maniruzzaman Manir, Kyungseok Park, Mee Kyung Sang, Surk-Sik Moon, Ho Won Jung
Cyclic dipeptides (CDPs) are one of the simplest compounds produced by living organisms. Plant-growth promoting rhizobacteria (PGPRs) also produce CDPs that can induce disease resistance. Bacillus vallismortis strain BS07 producing various CDPs has been evaluated as a potential biocontrol agent against multiple plant pathogens in chili pepper. However, plant signal pathway triggered by CDPs has not been fully elucidated yet. Here we introduce four CDPs, cyclo(Gly-L-Pro) previously identified from Aspergillus sp...
August 2017: Plant Pathology Journal
Lior Aram, Keren Yacobi-Sharon, Eli Arama
No abstract text is available yet for this article.
August 2017: Cell Death and Differentiation
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