In order to study the inherent difference among terpenes producing yeasts from the point of metabolomics, we selected taxadiene producing yeasts as the model system. The changes of cellular metabolites during fermentation log phase of artificial functional yeasts were determined using metabolomics methods. The results represented that compared to W303-1A as a blank control, the metabolites in glycolysis, tricarboxylic acid cycle (TCA) cycle and several amino acids were influenced. And due to the changes of metabolites, the growth of cells was inhibited to a certain extent. Among the metabolites identified, citric acid content in taxadiene producing yeasts changed the most, the decreasing amplitude reached 90% or more. Therefore, citric acid can be a marker metabolite for the future study of artificial functional yeasts. The metabolomics analysis of taxadiene producing yeasts can provide more information in further studies on optimization of terpenes production in heterologous chassis.
Alkenes ; metabolism ; Amino Acids ; metabolism ; Citric Acid ; analysis ; Citric Acid Cycle ; Diterpenes ; metabolism ; Fermentation ; Glycolysis ; Metabolome ; Metabolomics ; Yeasts ; metabolism

Erythromycin A is a clinically important macrolide antibiotic with broad-spectrum activity. Its biosynthesis involves the formation of the 14-membered skeleton catalyzed by polyketide synthases, and the modification steps such as hydroxylation, glycosylation and methylation. Based on the understanding of the biosynthetic mechanism, it is reliable to genetically manipulate the erythromycin A-producing strain for production improvement and structure modification. In this paper, we reviewed the progress regarding erythromycin A in high-producing strain construction and chemical structure derivation, to provide insights for further development.
Anti-Bacterial Agents ; biosynthesis ; chemistry ; Erythromycin ; biosynthesis ; chemistry ; Glycosylation ; Hydroxylation ; Methylation ; Multigene Family ; Polyketide Synthases ; metabolism

Gliomas are the most frequently occurring primary brain tumors in adults. Although they exist in different malignant stages, including histologically benign forms and highly aggressive states, most gliomas are clinically challenging for neuro-oncologists because of their infiltrative growth patterns and inherent relapse tendency with increased malignancy. Once this disease reaches the glioblastoma multiforme stage, the prognosis of patients is dismal: median survival time is 15 months. Extensive genetic analyses of glial tumors have revealed a variety of deregulated genetic pathways involved in DNA repair, apoptosis, cell migration/adhesion, and cell cycle. Recently, it has become evident that epigenetic alterations may also be an important factor for glioma genesis. Of epigenetic marks, histone modification is a key mark that regulates gene expression and thus modulates a wide range of cellular processes. In this review, I discuss the neuro-oncological significance of altered histone modifications and modifiers in glioma patients while briefly overviewing the biological roles of histone modifications.
Acetylation ; Adult ; Apoptosis ; Brain Neoplasms ; Cell Cycle ; DNA Repair ; Epigenomics ; Gene Expression ; Glioblastoma ; Glioma* ; Histones* ; Humans ; Methylation ; Prognosis ; Recurrence

Metabolic aberrations in the form of altered flux through key metabolic pathways are the major hallmarks of several life-threatening malignancies including malignant gliomas. These adaptations play an important role in the enhancement of the survival and proliferation of gliomas at the expense of the surrounding normal/healthy tissues. Recent studies in the field of neurooncology have directly targeted the altered metabolic pathways of malignant tumor cells for the development of anti-cancer drugs. Aerobic glycolysis due to elevated production of lactate from pyruvate regardless of oxygen availability is a common metabolic alteration in most malignancies. Aerobic glycolysis offers survival advantages in addition to generating substrates such as fatty acids, amino acids and nucleotides required for the rapid proliferation of cells. This review outlines the role of pyruvate dehydrogenase kinase (PDK) in gliomas as an inhibitor of pyruvate dehydrogenase that catalyzes the oxidative decarboxylation of pyruvate. An in-depth investigation on the key metabolic enzyme PDK may provide a novel therapeutic approach for the treatment of malignant gliomas.
Amino Acids ; Decarboxylation ; Dichloroacetic Acid ; Fatty Acids ; Glioma* ; Glycolysis ; Lactic Acid ; Metabolic Networks and Pathways ; Nucleotides ; Oxidoreductases* ; Oxygen ; Phosphotransferases* ; Pyruvic Acid*

OBJECTIVETo study influenza epidemic and analyze antigenic and genetic characterization of the predominant strains in Wuhan area in 2003.

METHODSEpidemiological data and specimens from influenza patients were collected from surveillance sites weekly. Viruses were isolated from the specimens. Three H3 isolates were chosen to do antigenic analysis by hemagglutination inhibition (HI) test and their HA1 region was sequenced.

RESULTSTotally 58 influenza viruses were isolated from 418 specimens, 57 of them were identified as H3 subtype and 1 of them was B subtype; both monthly positive rate and numbers of influenza like illness had two peaks of winter and summer, the highest peak appeared in July. The 3 new H3 isolates were antigenically different from vaccine strain A/Panama/2007/99, 14 amino acid changes have been found in HA1 domain of these 3 strains compared with A/Panama/2007/99, phylogenetic analysis also confirmed the difference in HA1 domain.

CONCLUSIONSInfluenza epidemic had two peaks in Wuhan area in 2003. The activity of H3 virus was strengthened remarkably. And they are antigenically and genetically different from the vaccine strain.

Amino Acid Sequence ; Antigens, Viral ; immunology ; China ; epidemiology ; Genes, Viral ; Glycosylation ; Hemagglutination Inhibition Tests ; Humans ; Influenza A Virus, H3N2 Subtype ; genetics ; immunology ; isolation & purification ; Influenza, Human ; epidemiology ; virology ; Molecular Sequence Data ; Phylogeny ; Sequence Analysis, Protein

Elution time of velogenic, mesogenic and lentogenic strains of Newcastle disease virus was determined. The differences in their elution time were also calculated. Four samples, each of a velogenic strain (VGF2), a mesogenic strain (Komarov) and a lentogenic strain (LaSota) were used for hemagglutination test with 0.6% chicken red blood cells. The time it took for wells of the end hemagglutination points (highest dilution that gave agglutination) to elute was recorded as elution time for each sample. The mean elution time of the three strains of Newcastle disease virus differed significantly (p < 0.05). The velogenic strain gave the highest mean elution time of 118 min, followed by the mesogenic strain with 59 min and the lentogenic strain with 25 min. Based on this result it appears that elution time could form a basis for rough characterization of isolates of Newcastle disease virus into the three major strains.
Animals ; Chickens/blood ; Erythrocytes/*virology ; Hemagglutination Tests ; *Hemagglutination, Viral ; Newcastle disease virus/isolation&purification/*pathogenicity

The gene encoding F protein of CBP-1 strain, a heat-stable Newcastle disease virus (NDV) isolated from the diseased pheasants in Korea, was characterized by reverse transcription-polymerase chain reaction (RT-PCR), nucleotide and amino acid sequences. Virus RNA was prepared from the chorioallatoic fluid infected with NDV CBP-1 virus and cDNA was amplified by RT-PCR, cloned and sequenced to analyze. The PCR was sensitive as to detect the virus titer above 25 hemagglutination unit. 1.7kb (1,707bp) size of the cDNA was amplified and cloned into BamHI site of pVL1393 Baculo transfer vector. The nucleotide sequences for F protein were determined by dye terminator cyclic sequencing using four pairs of primers, and 553 amino acid sequences were predicted. In comparison of the nucleotide sequence of F gene of CBP-1 with those of other NDV strains, the homology revealed 88.8%, 98.5% and 98.7% with Kyojungwon (KJW), Texas GB and Beaudette C strains, respectively. As the deduced 553 amino acid sequences of F protein of CBP-1 were compared with those of other NDV strains, the homology appeared 89.9%, 98.7% and 98.9% with KJW, Texas GB and Beaudette C strains, respectively. The putative protease cleavage site (112-116) was R-R-Q-K-R, indicating that CBP-1 strain is velogenic type. The amino acid sequences include 6 sites of N-asparagine-linked glycosylation and 13 cysteine residues. These data indicate that the genotype of CBP-1 strain is more closely associated with the strains of Texas GB and Beaudette C than KJW strain.
Amino Acid Sequence ; Animals ; Base Sequence* ; Clone Cells ; Cloning, Molecular* ; Cysteine ; DNA, Complementary ; Genotype ; Glycosylation ; Hemagglutination ; Korea ; Newcastle disease virus* ; Newcastle Disease* ; Polymerase Chain Reaction ; RNA ; Texas ; Viral Load

Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.
Acetylation ; Amino Acids ; Citric Acid Cycle ; Diabetes Mellitus, Type 2 ; Fatty Acids ; Glucose ; Glycolysis ; Metabolic Diseases ; Metabolic Networks and Pathways ; Metabolism* ; Mitochondria ; Neurodegenerative Diseases ; Obesity ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphoric Monoester Hydrolases ; Phosphorylation ; Phosphotransferases ; Protein Processing, Post-Translational ; Pyruvate Dehydrogenase Complex* ; Pyruvic Acid*

The 11-hydroxylation of 16alpha,17alpha-epoxy-4-pregenene-3,20-dione as a useful intermediate for the preparation of hormones can be achieved by the mycelium of Absidia coerulea at higher conversion rate than using other strains. In this paper 16alpha,17alpha-epoxy-4-pregenene-3,20-dione mixed with a little water, beta-cyclodextrin, Tween-80 was introduced into the fermentation broth after ultrasonication to increase pseudo-water-solubility of the hydrophobic substrate. This pseudo-crystallo feed could avoid the toxicity of organic solvents and was more available for the microbial transformation. The multi layer feed-forward neural network was used to setup a model which indicated the relationship between medium and feed components and the conversion rate. Particle swarm optimization (PSO), which was a stochastic global optimization algorithm and of which the convergence speed was high, was applied to obtain the optimal concentration of the medium and feed components. At optimum conditions with the pseudo-crystallo feed, the conversion rate of 16alpha,17alpha-epoxy-4-pregenene-3,20-dione at an initial concentration of 10 g/L was 87.5% in shaking flasks. The conversion rate of the substrate was up to 86.6% at higher concentration of 20 g/L feed in a 3.7 L fermentor.
Absidia ; metabolism ; Fermentation ; Hydroxylation ; Pregnenediones ; metabolism

The capability of utilizing the intermediates of TCA-cycle as the sole carbon source by the multi-vitamin auxotrophic yeast Torulopsis glabrata CCTCC M202019 under the conditions of vitamins limitation was demonstrated. Furthermore, the colony numbers grown on medium supplemented with glucose, acetate and one of the intermediates of TCA-cycle was higher than that of medium used glucose and acetate or medium used one of the intermediates of TCA-cycle carbon source. Among the intermediates of TCA-cycle used in this study, oxaloacetate was the best carbon source for the yeast and it was found that its presence stimulated the conversion of acetate to acetyl-CoA. In batch fermentation with glucose medium, the addition of 10 g/L of oxaloacetate improved the dry cell weight from 11.8 g/L to 13.6 g/L, and the productivity of pyruvate from 0.96 g x L(-1) x h(-1) to 1.19 g x L(-1) x h(-1), a 24% increase after 56 h growth. The yield of pyruvate on glucose was also improved as well, from 0.63 g/g to 0.66 g/g.
Candida glabrata ; growth & development ; metabolism ; Citric Acid Cycle ; Culture Media ; Fermentation ; Pyruvic Acid ; metabolism