Production of mannosylerythritol lipids as biosurfactants by resting cells ofCandida antarctica

Summary The resting cells ofCandida antarctica strain T-34 was found to produce a large amount of mannosylerythritol lipids as biosurfactants when incubated in the medium containing only the carbon source. The resting cells prepared from different water-soluble carbon sources were able to produce the lipids abundantly from water-insoluble carbon sources. Under the optimal conditions in a shake culture, the concentration of the total lipids amounted to about 47 g/l after 6 days, and the yield of the lipids became higher than that obtained by using the growing cells of the strain.     

Synthesis and biological evaluation of truncated α-galactosylceramide derivatives focusing on cytokine induction profile

A series of truncated analogs of α-galactosylceramide with altered ceramide moiety was prepared, and evaluated for Th2-biased response in the context of IL-4/IFN-γ ratio. Phytosphingosine-modified analogs including cyclic, aromatic and ethereal compounds as well as the C-glycoside analog of OCH (2) with their cytokine inducing profile are disclosed.     

Comparative analysis of the complete mitochondrial genomes of three rockfishes (Scorpaeniformes,Sebastiscus) and insights into the phylogenetic relationships of Sebastidae

Mitochondrial genome is a powerful molecule marker to provide information for phylogenetic relationships and revealing molecular evolution in ichthyological studies. Sebastiscus species, a marine rockfish, are of essential economic value. However, the taxonomic status and phylogenetic relationships of Sebastidae have been controversial so far. Here, the mitochondrial genomes (mitogenomes) of three species, S. tertius, S. albofasciatus, and S. marmoratus, were systemically investigated. The lengths of the mitogenomes’ sequences of S. tertius, S. albofasciatus, and S. marmoratus were 16910, 17056, and 17580 bp, respectively. It contained 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), 22 transfer RNA (tRNA) genes, and one identical control region (D-loop) among the three species. The genetic distance and K_a/K_s ratio analyses indicated 13 PCGs were suffering purifying selection and the selection pressures were different from certain deep-sea fishes, which were most likely due to the difference in their living environment. The phylogenetic tree was constructed by Bayesian Inference (BI) and Maximum Likelihood (ML). Most interestingly, the results indicated that Sebastidae and Scorpaenidae were grouped into a separate branch, so the taxonomic status of Sebastidae should be classified into subfamily Sebastinae. Our results may lead to a taxonomic revision of Scorpaenoidei.     

Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors

Fe(II)/α-ketoglutarate-dependent lysine demethylases (KDMs) are attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone H3 level, suggesting KDM5 inhibition in the cells.     

Diurnal changes in needle gas exchange in alpine Pinus pumila during snow-melting and summer seasons

Pinus pumila (Pallas) Regel. is a dominant dwarf tree in alpine regions of Japan. The possible factors limiting the net photosynthetic rate (P_n) of the needles of P. pumila were examined in the snow-melting (May) and the summer (August) seasons. In August, in situ maximum P_n was 20 mol kg^–1 needle s^–1 in the current-year needles and 25 mol kg^–1 needle s^–1 in the 1-year-old needles. Diurnal trends of P_n in August were positively related to fluctuations in photosynthetic photon flux density (PPFD) and no midday depression of P_n was found, indicating that a decrease in PPFD rather than an increase in needle-to-air vapor pressure deficit (W) might cause the reduction of P_n. Both stomatal conductance (g_s) and P_n were lower in May than in August. In May, P_n and g_s were almost zero in the morning, but gradually increased with decreasing W, reaching maximum P_n values (4 mol kg^–1 needle s^–1) and g_s (60 mmol kg^–1 needle s^–1) at 16.00 hours. The daytime P_n in May was positively related to g_s. Relative water content in the exposed needles above the snow in May was 83%, which was far above the lethal level. This indicates that the water flow from stems or soils to needles was enough to compensate for a small amount of water loss due to the low g_s in May, although the water supplied to needles would be impeded by the low temperatures. Thus, the reduced g_s in May would be important for avoiding needle desiccation, and would result in a reduced P_n.     

Discovery of TAK-960: An orally available small molecule inhibitor of polo-like kinase 1 (PLK1)

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.     

Roles of Long-range Electrostatic Domain Interactions and K+ in Phosphoenzyme Transition of Ca2+-ATPase

Sarcoplasmic reticulum Ca²⁺-ATPase couples the motions and rearrangements of three cytoplasmic domains (A, P, and N) with Ca²⁺ transport. We explored the role of electrostatic force in the domain dynamics in a rate-limiting phosphoenzyme (EP) transition by a systematic approach combining electrostatic screening with salts, computer analysis of electric fields in crystal structures, and mutations. Low KCl concentration activated and increasing salt above 0.1 m inhibited the EP transition. A plot of the logarithm of the transition rate versus the square of the mean activity coefficient of the protein gave a linear relationship allowing division of the activation energy into an electrostatic component and a non-electrostatic component in which the screenable electrostatic forces are shielded by salt. Results show that the structural change in the transition is sterically restricted, but that strong electrostatic forces, when K⁺ is specifically bound at the P domain, come into play to accelerate the reaction. Electric field analysis revealed long-range electrostatic interactions between the N and P domains around their hinge. Mutations of the residues directly involved and other charged residues at the hinge disrupted in parallel the electric field and the structural transition. Favorable electrostatics evidently provides a low energy path for the critical N domain motion toward the P domain, overcoming steric restriction. The systematic approach employed here is, in general, a powerful tool for understanding the structural mechanisms of enzymes.     

Metabolic and morphological changes of an oil accumulating trebouxiophycean alga in nitrogen-deficient conditions

Oil-rich algae have promising potential for a next-generation biofuel feedstock. Pseudochoricystis ellipsoidea MBIC 11204, a novel unicellular green algal strain, accumulates a large amount of oil (lipids) in nitrogen-deficient (–N) conditions. Although the oil bodies are easily visualized by lipophilic staining in the cells, little is known about how oil bodies are metabolically synthesized. Clarifying the metabolic profiles in –N conditions is important to understand the physiological mechanisms of lipid accumulations and will be useful to optimize culture conditions efficiently produce industrial oil. Metabolome and lipidome profiles were obtained, respectively, using capillary electrophoresis- and liquid chromatography-mass spectrometry from P. ellipsoidea in both nitrogen-rich (+N; rapid growth) and –N conditions. Relative quantities of more than 300 metabolites were systematically compared between these two conditions. Amino acids in nitrogen assimilation and N-transporting metabolisms were decreased to 1/20 the amount, or less, in –N conditions. In lipid metabolism, the quantities of neutral lipids increased greatly in –N conditions; however, quantities of nearly all the other lipids either decreased or only changed slightly. The morphological changes in +N and –N conditions were also provided by microscopy, and we discuss their relationship to the metabolic changes. This is the first approach to understand the novel algal strain’s metabolism using a combination of wide-scale metabolome analysis and morphological analysis.