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Kaikai Zhu, Hui Liu, Xinlu Chen, Qunkang Cheng, Zong-Ming Max Cheng
BACKGROUND: Crassulacean acid metabolism (CAM) plants use water 20-80% more efficiently by shifting stomata opening and primary CO2 uptake and fixation to the nighttime. Protein kinases (PKs) play pivotal roles in this biological process. However, few PKs have been functionally analyzed precisely due to their abundance and potential functional redundancy (caused by numerous gene duplications). RESULTS: In this study, we systematically identified a total of 758 predicted PK genes in the genome of a CAM plant, pineapple (Ananas comosus)...
September 18, 2018: BMC Plant Biology
René Benndorf, Huijuan Guo, Elisabeth Sommerwerk, Christiane Weigel, Maria Garcia-Altares, Karin Martin, Haofu Hu, Michelle Küfner, Z Wilhelm de Beer, Michael Poulsen, Christine Beemelmanns
The chemical analysis of insect-associated Actinobacteria has attracted the interest of natural product chemists in the past years as bacterial-produced metabolites are sought to be crucial for sustaining and protecting the insect host. The objective of our study was to evaluate the phylogeny and bioprospecting of Actinobacteria associated with fungus-growing termites. We characterized 97 Actinobacteria from the gut, exoskeleton, and fungus garden (comb) of the fungus-growing termite Macrotermes natalensis and used two different bioassays to assess their general antimicrobial activity...
September 13, 2018: Antibiotics
Manar El Samak, Samar M Solyman, Amro Hanora
Marine invertebrates-associated microorganisms were considered to be important sources of marine bioactive products. This study aims to isolate marine invertebrates associated bacteria with antimicrobial activity from the Red Sea and test their biosynthetic potential through the detection of PKS and NRPS gene clusters involved with the production of bioactive secondary metabolites. In this respect, fifty bacterial strains were isolated from eight different Red Sea marine invertebrates and screened for their antimicrobial activity against standard pathogenic bacteria ( Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633) and yeast ( Candida albicans ATCC 10231) using the standard well diffusion assay...
September 2018: Biotechnology Reports
H-T Arkenau, A Italiano, G Mak, M Toulmonde, R D Baird, J Garcia-Corbacho, R Plummer, M Flynn, M Forster, R H Wilson, D Tosi, A Adenis, K Donaldson, J Posner, I Kawabata, A Arimura, S Deva, J Spicer
BACKGROUND: Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2 inhibitor, has established a recommended daily dose of 800 mg in patients with solid tumours. In this study, we have recruited a larger number of patients to assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour activity. PATIENTS AND METHODS: Patients with solid tumours expressing EGFR or HER2 received a single dose of epertinib at 800 mg on Day 1 to assess PK over 7 days, followed by continuous once-daily dosing from Day 8...
September 6, 2018: European Journal of Cancer
Greg J Dodge, Finn P Maloney, Janet L Smith
Covering: up to the end of 2018Polyketides are a valuable source of bioactive and clinically important molecules. The biosynthesis of these chemically complex molecules has led to the discovery of equally complex polyketide synthase (PKS) pathways. Crystallography has yielded snapshots of individual catalytic domains, di-domains, and multi-domains from a variety of PKS megasynthases, and cryo-EM studies have provided initial views of a PKS module in a series of defined biochemical states. Here, we review the structural and biochemical results that shed light on the protein-protein interactions critical to catalysis by PKS systems with an embedded acyltransferase...
September 6, 2018: Natural Product Reports
Greg J Dodge, Danialle Ronnow, Richard E Taylor, Janet L Smith
Polyketide synthases (PKS) are a rich source of natural products of varied chemical composition and biological significance. Here, we report the characterization of an atypical dehydratase (DH) domain from the PKS pathway for gephyronic acid, an inhibitor of eukaryotic protein synthesis. Using a library of synthetic substrate mimics, the reaction course, stereospecificity, and tolerance to non-native substrates of GphF DH1 are probed via LC-MS analysis. Taken together, the studies establish GphF DH1 as a dual-function dehydratase/isomerase that installs an odd-to-even double bond and yields a product consistent with the isobutenyl terminus of gephyronic acid...
September 21, 2018: ACS Chemical Biology
Satoshi Yuzawa, Amin Zargar, Bo Pang, Leonard Katz, Jay D Keasling
Reduced polyketides are a subclass of natural products that have a variety of medical, veterinary, and agricultural applications and are well known for their structural diversity. Although these compounds do not resemble each other, they are all made by a class of enzymes known as modular polyketide synthases (PKSs). The commonality of PKS domains/modules that compose PKSs and the understanding of the relationship between the sequence of the PKS and the structure of the compound it produces render modular PKSs as excellent targets for engineering to produce novel compounds with predicted structures...
2018: Methods in Enzymology
Rima Kaddurah-Daouk, Thomas Hankemeier, Elizabeth H Scholl, Rebecca Baillie, Amy Harms, Claus Stage, Kim P Dalhoff, Gesche Jűrgens, Olivier Taboureau, Grace S Nzabonimpa, Alison A Motsinger-Reif, Ragnar Thomsen, Kristian Linnet, Henrik B Rasmussen
Carboxylesterase 1 (CES1) metabolizes methylphenidate and other drugs. CES1 gene variation only partially explains pharmacokinetic (PK) variability. Biomarkers predicting the PKs of drugs metabolized by CES1 are needed. We identified lipids in plasma from 44 healthy subjects that correlated with CES1 activity as determined by PK parameters of methylphenidate including a ceramide (q value = 0.001) and a phosphatidylcholine (q value = 0.005). Carriers of the CES1 143E allele had decreased methylphenidate metabolism and altered concentration of this phosphatidylcholine (q value = 0...
August 2018: CPT: Pharmacometrics & Systems Pharmacology
Takayoshi Awakawa, Takuma Fujioka, Lihan Zhang, Shotaro Hoshino, Zhijuan Hu, Junko Hashimoto, Ikuko Kozone, Haruo Ikeda, Kazuo Shin-Ya, Wen Liu, Ikuro Abe
Reprogramming of the NRPS/PKS assembly line is an attractive method for the production of new bioactive molecules. However, it is usually hampered by the loss of intimate domain/module interactions required for the precise control of chain transfer and elongation reactions. In this study, we first establish heterologous expression systems of the unique antimycin-type cyclic depsipeptides: JBIR-06 (tri-lactone) and neoantimycin (tetra-lactone), and engineer their biosyntheses by taking advantage of bioinformatic analyses and evolutionary insights...
August 30, 2018: Nature Communications
Guodong Yang, Peng Li, Lifen Meng, Keyi Xv, Faming Dong, Yan Qiu, Lei He, Lin Lin
To know more about the potential roles of endophytic fungi in the formation mechanism of Daodi medicinal material, diversity and communities of culturable endophytic fungi in three types of tree peonies were investigated. Endophytic fungi of three types of tree peonies were isolated and identified. The diversity was analyzed. Bayesian trees constructed by MrBayes 3.2.6 after phylogenetic analysis of the ITS sequences. The endophytic fungi potential for synthesis of natural products was assessed by means of detecting NRPS and PKS gene sequences...
August 17, 2018: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
Rasmus J N Frandsen, Paiman Khorsand-Jamal, Kenneth T Kongstad, Majse Nafisi, Rubini M Kannangara, Dan Staerk, Finn T Okkels, Kim Binderup, Bjørn Madsen, Birger Lindberg Møller, Ulf Thrane, Uffe H Mortensen
The natural red food colorants carmine (E120) and carminic acid are currently produced from scale insects. The access to raw material is limited and current production is sensitive to fluctuation in weather conditions. A cheaper and more stable supply is therefore desirable. Here we present the first proof-of-concept of heterologous microbial production of carminic acid in Aspergillus nidulans by developing a semi-natural biosynthetic pathway. Formation of the tricyclic core of carminic acid is achieved via a two-step process wherein a plant type III polyketide synthase (PKS) forms a non-reduced linear octaketide, which subsequently is folded into the desired flavokermesic acid anthrone (FKA) structure by a cyclase and a aromatase from a bacterial type II PKS system...
August 27, 2018: Scientific Reports
Lin Li, Linhuan Huang, Xuan Huang, Shaobin Lin, Zhiming He, Qun Fang
Pallister-Killian syndrome (PKS) is often incidentally diagnosed prenatally due to ultrasound abnormalities or advanced maternal age. Severely shortened limbs could be the most outstanding abnormal observation in a fetus with PKS. PKS can be detected with the highest mosaic ratio by chromosomal microarray analysis (CMA) on uncultured amniocytes prenatally.
August 2018: Clinical Case Reports
Birsen Karaman, Hülya Kayserili, Asadollah Ghanbari, Zehra Oya Uyguner, Güven Toksoy, Umut Altunoglu, Seher Basaran
Background: Pallister Killian syndrome (PKS, OMIM 601803) is a rare genetic disorder with a distinct phenotype caused by tissue- limited mosaicism tetrasomy of the short arm of chromosome 12, which usually cytogenetically presents as an extra isochromosome 12p.Wide phenotypic variability in PKS has been reported, ranging from pre-to perinatal death due to multiple congenital anomalies, especially diaphragmatic hernia, and classic phenotypes including seizures, severe developmental delay, macrosomia at birth, deafness, and distinct dysmorphic features, such as coarse face, temporal alopecia, a small nose with anteverted nostrils, long philtrum, and hypo-/hyper- pigmented streaks on the skin...
2018: Molecular Cytogenetics
In Jeong Kang, Hyeong Kwon Shim, Jae Hwan Roh, Sunggi Heu, Dong Bum Shin
Northern corn leaf spot and southern corn leaf blight caused by Cochliobolus carbonum (anamorph, Bipolaris zeicola ) and Cochliobolus heterostrophus (anamorph, Bipolaris maydis ), respectively, are common maize diseases in Korea. Accurate detection of plant pathogens is necessary for effective disease management. Based on the polyketide synthase gene (PKS) of Cochliobolus carbonum and the nonribosomal peptide synthetase gene (NRPS) of Cochliobolus heterostrophus , primer pairs were designed for PCR to simultaneously detect the two fungal pathogens and were specific and sensitive enough to be used for duplex PCR analysis...
August 2018: Plant Pathology Journal
Meenakshi Kagda, Andrea L Vu, Audrey M V Ah-Fong, Howard S Judelson
Flagellated spores play important roles in the infection of plants and animals by many eukaryotic microbes. The oomycete Phytophthora infestans, which causes potato blight, expresses two phosphagen kinases (PKs). These enzymes store energy in taurocyamine, and are hypothesized to resolve spatial and temporal imbalances between rates of ATP creation and use in zoospores. A dimeric PK is found at low levels in vegetative mycelia, but high levels in ungerminated sporangia and zoospores. In contrast, a monomeric PK protein is at similar levels in all tissues, although is transcribed primarily in mycelia...
August 23, 2018: Molecular Microbiology
Dominik A Herbst, Craig A Townsend, Timm Maier
Covering: up to mid of 2018Type I fatty acid synthases (FASs) are giant multienzymes catalyzing all steps of the biosynthesis of fatty acids from acetyl- and malonyl-CoA by iterative precursor extension. Two strikingly different architectures of FAS evolved in yeast (as well as in other fungi and some bacteria) and metazoans. Yeast-type FAS (yFAS) assembles into a barrel-shaped structure of more than 2 MDa molecular weight. Catalytic domains of yFAS are embedded in an extensive scaffolding matrix and arranged around two enclosed reaction chambers...
August 23, 2018: Natural Product Reports
Zhipeng Li, Xi Chen, Jun Li, Tong Meng, Lingwei Wang, Zhen Chen, Yanyan Shi, Xueping Ling, Weiang Luo, Dafeng Liang, Yinghua Lu, Qingbiao Li, Ning He
Schizochytrium sp. is a kind of marine microalgae with great potential as promising sustainable source of polyunsaturated fatty acids (PUFAs). Polyketide synthase-like (PKS synthase) is supposed to be one of the main ways to synthesize PUFAs in Schizochytrium sp. In order to study the exact relationship between PKS and PUFA biosynthesis, chain length factor (CLF) and dehydrogenase (DH) were cloned from the PKS gene cluster in Schizochytrium sp., then disrupted by homologous recombination. The results showed that DH- and CLF-disrupted strains had significant decreases (65...
August 22, 2018: Marine Biotechnology
Limin Wang, Jing Jin, Xiao Liu, Yan Wang, Yang Liu, Yueju Zhao, Fuguo Xing
Ochratoxin A (OTA) is a potent nephrotoxic, hepatotoxic, and teratogenic compound which is a significant mycotoxin contaminates cereals during storage. Aspergillus ochraceus is the most common producer of OTA in cereals and cereal-derived products. Cinnamaldehyde is a natural substance derived from plant cinnamon playing an important role in the reduction of OTA contamination. In this study, the antifungal and antitoxigenic effect of cinnamaldehyde was investigated with its mechanisms of inhibition of fungal growth at the morphological and ultrastructural levels, and inhibition of OTA biosynthesis at the transcriptional level...
August 22, 2018: Toxins
Jie-Jie Shen, Fu Chen, Xiao-Xuan Wang, Xiao-Fang Liu, Xin-Ai Chen, Xu-Ming Mao, Yong-Quan Li
Acyltransferase domains (ATs) of polyketide synthases (PKSs) are critical for loading of acyl groups on acyl carrier protein domains (A) via self - and trans -acylation reactions, to produce structurally diverse polyketides. However, the interaction specificity between ATs and unusual acyl units is rarely documented. In Streptomyces tsukubaensis YN06, we found that AT4FkbB [an AT in the fourth module of tacrolimus (FK506) PKS] transferred both allylmalonyl (allmal) and emthylmalonyl (ethmal) units to ACPs, which was supposed responsible for the production of both FK506 and its analog FK520, respectively...
2018: Frontiers in Microbiology
Mi Hye Kwon, Jin Seok Jeong, Jayoung Ryu, Young Woong Cho, Hee Eun Kang
DA-9805 is a botanical anti-Parkinson's drug candidate formulated from ethanol extracts of the root of Bupleurum falcatum , the root cortex of Paeonia suffruticosa , and the root of Angelica dahurica . The pharmacokinetics (PKs) and brain distribution of active/representative ingredients of DA-9805, Saikosaponin a (SSa; 1.1⁻4.6 mg/kg), Paeonol (PA; 14.8⁻59.2 mg/kg), and Imperatorin (IMP; 1.4⁻11.5 mg/kg) were evaluated following the intravenous or oral administration of each pure component and the equivalent dose of DA-9805 in rats...
August 20, 2018: Pharmaceutics
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