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In Ce3+ activated SrLn2O4 type phosphors (Ln = Y, Lu, Sc, etc.) only one Ce3+ center was previously reported to show a blue emission band. In this paper, we report the observation of a second Ce3+ center in SrLu2O4:Ce3+. The new center shows a red emission band peaking at 600 nm with an excitation band at 485 nm. We attributed the new center (Ce(II)) to the substitution of the Lu3+ site and the original blue center (Ce(I)) to the substitution of the Sr2+ site. Spectroscopy studies indicate that Ce(I) centers are preferentially formed at a low doping concentration and the number ratio of Ce(I)/Ce(II) decreases with increasing Ce3+ concentration until beyond 0.002. The fluorescence lifetimes of the two centers were measured for various doping concentrations. Energy transfer from Ce(I) to Ce(II) was observed. It was found that the emission intensity of Ce(II) centers reduces much faster than that of Ce(I) with increasing temperature from 83 K up to 350 K, implying their potential application in temperature sensing based on their temperature dependent intensity ratios. A relative sensing sensitivity as high as 2.28% K−1 at 283 K was achieved.

International audience; With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Nature forms S-S bonds by oxidizing two sulfhydryl groups, and no enzyme installing an intact hydropersulfide (-SSH) group into a natural product has been identified to date. The leinamycin (LNM) family of natural products features intact S-S bonds, and previously we reported an SH domain (LnmJ-SH) within the LNM hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line as a cysteine lyase that plays a role in sulfur incorporation. Here we report the characterization of an S-adenosyl methionine (SAM)-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin (GNM) biosynthesis, discovery of hydropersulfides as the nascent products of the GNM and LNM hybrid NRPS-PKS assembly lines, and revelation of three SH domains (GnmT-SH, LnmJ-SH, and WsmR-SH) within the GNM, LNM, and weishanmycin (WSM) hybrid NRPS-PKS assembly lines as thiocysteine lyases. Based on these findings, we propose a biosynthetic model for the LNM family of natural products, featuring thiocysteine lyases as PKS domains that directly install a -SSH group into the GNM, LNM, or WSM polyketide scaffold. Genome mining reveals that SH domains are widespread in Nature, extending beyond the LNM family of natural products. The SH domains could also be leveraged as biocatalysts to install an -SSH group into other biologically relevant scaffolds., Enzymes installing an intact hydropersulfide (-SSH) group into natural products have so far not been identified. Here, the authors report the characterization of an S-adenosyl methionine-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin biosynthesis, and identification of three SH domains within several NRPS-PKS assembly lines as thiocysteine lyases.

The efficient utilization of both glucose and xylose, the two most abundant sugars in biomass hydrolysates, is one of the main objectives of biofermentation with lignocellulosic materials. The utilization of xylose is commonly inhibited by glucose, which is known as glucose catabolite repression (GCR). Here we report a GCR-based dynamic control (GCR-DC) strategy aiming at a better co-utilization of glucose and xylose, by decoupling the cell growth and biosynthesis of riboflavin as a product. Using the thermophilic strain Geobacillus thermoglucosidasius DSM2542 as a host, we constructed extra riboflavin biosynthetic pathways that were activated by xylose but not glucose. The engineered strains showed a two-stage fermentation process. In the first stage, glucose was preferentially used for cell growth and no production of riboflavin was observed, while in the second stage where glucose was nearly depleted, xylose was effectively utilized for riboflavin biosynthesis. Using the corn cob hydrolysate as a carbon source, the optimized riboflavin yields of strains DSM2542-DCall-MSS (full pathway dynamic control strategy) and DSM2542-DCrib (single module dynamic control strategy) were 5.26 and 2.26 folds higher than that of the control strain DSM2542 Rib-Gtg constitutively producing riboflavin, respectively. This GCR-DC strategy should also be applicable to the construction of cell factories that can efficiently use natural carbon sources with multiple sugar components for the production of high-value chemicals in future.

Near-infrared (NIR) to visible upconversion (UC) luminescence in activator Er3+ and sensitizer Yb3+ codoped systems has been extensively studied. In this work, we report the results of Er3+-sensitized Yb3+ NIR UC emission at similar to 1000 nm originating from 2F5/2 -> 2F7/2 transition under infrared (IR) excitation at similar to 1500 nm responsible for Er3+ 4I15/2 -> 4I13/2 transition absorption. The IR to NIR UC is a desirable strategy to increase solar light utilization by reducing the spectral mismatch between the solar spectrum and crystalline silicon (c-Si) solar cells. Er3+ singly doped phosphors are mostly used for realizing the IR to NIR UC emission derived from Er3+ 4I11/2 -> 4I15/2 transition centered also at similar to 1000 nm. The efficiency of this transition, however, is limited by multiphonon relaxation and radiative transition to the 4I13/2 state. Here, Yb3+ ions are codoped in Y2O3:Er3+, and NIR UC emission with the intensity enhanced 1.5 times is achieved due to efficient energy transfer from Er3+ to Yb3+ and highly efficient Yb3+ emission. The influence of the dopants' concentrations on UC dynamics is studied. The optimal concentration under IR excitation is 5% Er3+ and 1% Yb3+. Our results indicate that introducing Yb3+ ions in Er3+ singly doped phosphors may notably improve the IR to NIR UC performance.

Er3+ and Yb3+ codoped Gd2Mo4O15 upconversion (UC) phosphors are synthesized by high temperature solid state reaction. The crystalline phase and morphology are studied in detail by X-ray diffraction (XRD), Raman spectroscopy and scanning electron microscopy (SEM). Under 980 nm laser excitation, the phosphors show a significant green UC luminescence contributed from 2H11/2/4S3/2 → 4I15/2 transitions of Er3+, while the popular red 4F9/2 → 4I15/2 emission is quite weak. The temporal evolutions of Er3+ and Yb3+ emissions after 980 nm pulse excitation are studied as a function of Er3+ and Yb3+ concentrations. It is revealed that the weak red UC emission is due to its low emission efficiency in Gd2Mo4O15 that has a high cutoff phonon energy of 960 cm−1. The temperature sensing behaviors based on the thermally coupled 2H11/2 and 4S3/2 levels have been explored. A high absolute sensitivity of 0.00853 K−1 at 554 K is achieved and an excellent thermal durability is observed. The relative absorptance of 4I15/2 → 2H11/2 transition to the 4I15/2 → 4S3/2 transition is proposed as a good measure for evaluating the absolute sensitivity based on the comparative study of some familiar materials. Our results imply that Gd2Mo4O15 is a promising green UC phosphor for optical thermometry.

Blue-emitting phosphors for near ultraviolet (NUV) based tri-color RGB phosphor blend converted white light emitting diodes (LEDs) have been extensively investigated in the past few years. LED chip peaked near 400 nm is the most efficient among the NUV chips currently. However, most of blue phosphors show inefficient excitation around 400 nm. Herein, a novel blue phosphor SrLu2O4:Ce3+ matching well with near 400 nm chip and showing high thermal stability has been developed. The photoluminescence spectrum presents a broad emission band peaking at 460 nm with a bandwidth of nearly 90 nm. By optimizing the Ce3+ concentration, an internal quantum efficiency (IQE) as high as 76% was achieved. Furthermore, 86% of the room-temperature emission intensity is still maintained at 150 °C, indicating a good thermal stability and practicality. A series of white LEDs were fabricated based on 405 nm chips coated with a blend of the new blue phosphor with the commercial yellow and red phosphors. High color rendering indexes (≥90) were achieved while the correlated color temperature was tuneable in the range of 3094 to 8990 K. These results suggest that SrLu2O4:Ce3+ can be utilized as a blue-emitting phosphor in NUV based white LEDs.

CaSc2O4 phosphors codoped with 0.2% Er3+ and various concentrations (0–15%) of Yb3+ are prepared by high temperature solid-state reaction. Two Er3+ luminescence centers are observed and they are assigned to substitution for Ca2+ site (Er3+(I)) and Sc3+ site (Er3+(II)), respectively. We find that the Er3+(I) centers are preferentially formed at low doping concentration and their number starts to decrease along with the increase of the Er3+(II) centers on increasing Yb3+ concentration. Meanwhile, intense upconversion luminescence (UCL) with color tuning from green to red is observed upon 980 nm excitation. The decomposition of the UCL spectra exhibits the main contribution from the Er3+(I) centers in the range of Yb3+ concentration of this work. This result is attributed to efficient emissions of the Er3+(I) centers for the long lifetimes of Er3+(I) both on the green and red emitting levels. Furthermore, we have observed the UCL intensity of CaSc2O4: 0.2% Er3+, 15% Yb3+ is 4 times as strong as that in Y2O3: 0.2 Er3+, 15% Yb3+.

The dehydratase domains (DHs) of the iso-migrastatin (iso-MGS) polyketide synthase (PKS) were investigated by systematic inactivation of the DHs in module-6, -9, -10 of MgsF (i.e., DH6, DH9, DH10) and module-11 of MgsG (i.e., DH11) in vivo, followed by structural characterization of the metabolites accumulated by the mutants, and biochemical characterization of DH10 in vitro, using polyketide substrate mimics with varying chain lengths. These studies allowed us to assign the functions for all four DHs, identifying DH10 as the dedicated dehydratase that catalyzes the dehydration of the C17 hydroxy group during iso-MGS biosynthesis. In contrast to canonical DHs that catalyze dehydration of the β-hydroxy groups of the nascent polyketide intermediates, DH10 acts in a long-range manner that is unprecedented for type I PKSs, a novel dehydration mechanism that could be exploited for polyketide structural diversity by combinatorial biosynthesis and synthetic biology.

Emission spectra of Tm 3+ and Yb 3+ codoped Lu 2 O 3 are studied as a function of the dopant concentration upon 980 nm excitation. The upconverted near infrared emission around 811 nm from Tm 3+ : 3 H 4 → 3 H 6 transition is observed due to two step energy transfers from Yb 3+ through Tm 3+ : 3 F 4 as the intermediate level. The optimal dopants concentrations for the strongest upconversion emission are 0.1 mol% Tm 3+ and 4 mol% Yb 3+ . The dependence of energy transfer coefficients for the two step energy transfers on Tm 3+ and/or Yb 3+ concentration is studied. The obtained results indicate that the excitation diffusions among Yb 3+ ions and among Tm 3+ ions mainly control the energy transfer rates for the optimal dopants concentrations and thus dominate the energy transfer upconversion process.

Near-infrared downconversion phenomenon has been demonstrated in Lu2O3: Tm3+/Yb3+ phosphor upon direct excitation of Tm3+:1G4 level at 463 nm. The efficient energy transfer from Tm3+: 1G4 → Yb: 2F5/2 has been elucidated by the excitation spectra, the visible and NIR spectra as well as the decay curves of Tm: 1G4 state. The mechanism of downconversion in Lu2O3:Tm3+/Yb3+ has been discussed in detail. According to analysis of the dependence of the initial transfer rate over Yb3+ ion concentration, it could be included that energy transfer (ET) from Tm3+ to Yb3+ is a single-step ET process instead of a cooperative one. By varying the Yb3+ concentrations, we obtain the Lu2O3: 0.2%Tm3+/30%Yb3+ sample with theoretical quantum efficiency as high as 148.2%. Because the excited state of Yb3+ just above the band edge of crystalline silicon, it suggested that Lu2O3: Tm3+/Yb3+ sample will be beneficial to improve the conversion efficiency of c-Si solar cells.

Under 808 nm excitation into the Tm3+:3H4 level, a considerable enhancement in intensity of Tm3+: 3F4→3H6 emission with respect to Tm3+: 3H4→3F4 emission is observed in Tm3+/Yb3+ codoped Lu1.6Sc0.4O3. The Tm3+-Yb3+-Tm3+ forward-backward energy transfer is proved to generate an additional route for the 3H4→3F4 nonradiative relaxation, that is, energy transfer from Tm3+:3H4 to Yb3+:2F5/2 and the subsequent back transfer from Yb3+:2F5/2 to Tm3+:3F4. The analysis of emission spectra reveals that back transfer from Yb3+ that excited by the forward energy transfer is more efficient than by absorption of 980 nm infrared light. The efficiency can reach as high as 96% with an extremely low Tm3+ concentration (0.05%). We propose that those Yb3+ ions with nearby Tm3+ ions in the forward energy transfer are preferentially excited instead of equally excited as by absorption of light. The efficiencies of the energy back transfer at different Yb3+ concentrations are evaluated, indicating that the forward-backward energy transfer can act as a dominant route for the Tm3+: 3H4→3F4 nonradiative relaxation when Yb3+ concentration is higher than 5%. A method to determine the radiative rate of Tm3+:3H4 state based on the model of cross relaxation is also demonstrated.

Bacterial natural products and their analogues constitute more than half of the new small molecule drugs developed over the last several decades. Despite this success, interest in natural products from major pharmaceutical companies has decreased even as genomics has uncovered the large number of biosynthetic gene clusters (BGCs) that encode for novel natural products. To date though, there is still a lack of universal strategies and enabling technologies to discover natural products at scale and speed. This review highlights several of the opportunities provided by genome sequencing and bioinformatics, challenges associated with translating genomes into natural products, and examples of successful strain prioritization and BGC activation strategies that have been used in the genomic era for natural product discovery from cultivatable bacteria.

Isofuranonaphthoquinones (IFQs) and Isoindolequinones (IIQs) comprise a small family of natural products, with the latter ones are especially uncommon in nature. Here we report the discovery of seven new IFQs, IFQ A-G (1-7), and three new IIQs, IIQ A-C (8-10), along with the known anthraquinone desoxyerythrolaccin (11), from Streptomyces sp. CB01883, expanding the chemical diversity of this family of natural products. The structures of these natural products were established on the basis of their HR-ESI-MS and nuclear magnetic resonance (NMR) spectroscopic data. All compounds were assessed for antibacterial activity, with 11 and 1, 5-7 exhibiting moderate and weak activities, respectively, against several Gram-positive bacteria tested. Bioinformatics analysis of the Streptomyces sp. CB01883 genome revealed the ifq gene cluster that showed identical genetic organization, with high-sequence identity, to the ifn gene cluster recently cloned from Streptomyces sp. RI-77 and confirmed to encode the biosynthesis of two IFQs, JBIR-76 and JBIR-77. Co-isolation of IFQs with IIQs from Streptomyces sp. CB01883 and facile chemical transformation of selected IFQs to IIQs, as exemplified by 1 to 9, together with the finding of the ifq cluster that most likely only encodes IFQ biosynthesis, support the proposal that IIQs may be derived nonenzymatically from IFQs in the presence of an amine.

The Yb(3+) and Er(3+) codoped orthorhombic LuF3 rectangular nanocrystals (NCs) with the size of about 10nm were synthesized by a facile and effective solvothermal process. X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), upconversion (UC) luminescence spectra and decay curves were used to characterize the resulting samples. Compared with YF3 and α-NaYF4 NCs, owning the similar size and the same doping levels of Yb(3+) ions and Er(3+) ions as LuF3 NCs, the green UC emission of LuF3 NCs is 18.7 times and 5.1 times stronger than that of YF3 and α-NaYF4 NCs respectively; the red UC emission of LuF3 NCs is 13.2 times and 0.6 times stronger than that of YF3 and α-NaYF4 NCs respectively. Under 980 nm wavelength excitation, the decay curves of both (4)S3/2→(4)I15/2 transition and (4)F9/2→(4)I15/2 transition exhibit a single exponential function, resulting from the fast energy migrations among Yb(3+) ions caused by the high concentration of Yb(3+) ions (20 mol%). Meanwhile, at relatively low power density, the slopes of the linear plots between log(I) and log(P) for green UC and red UC are 1.7 and 1.9 respectively, which are less than 2 due to the quenching of the thermal effect, indicating a two-photon process for them. At high power density, the slopes are decreased caused by the saturation effect. In addition, we proved the existence of the thermal effect by the pump power dependence of the intensity ratio of (2)H11/2→(4)I15/2 transition to (4)S3/2→(4)I15/2 transition.

Leinamycin (LNM) is a potent antitumor antibiotic produced by Streptomyces atroolivaceus S-140. Both in vivo and in vitro characterization of the LNM biosynthetic machinery have established the formation of the 18-membered macrolactam backbone and the C-3 alkyl branch; the nascent product, LNM E1, of the hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide synthase (PKS); and the generation of the thiol moiety at C-3 of LNM E1. However, the tailoring steps converting LNM E1 to LNM are still unknown. Based on gene inactivation and chemical investigation of three mutant strains, we investigated the tailoring steps catalyzed by two cytochromes P450 (P450s), LnmA and LnmZ, in LNM biosynthesis. Our studies revealed that (i) LnmA and LnmZ regio- and stereoselectively hydroxylate the C-8 and C-4′ positions, respectively, on the scaffold of LNM; (ii) both LnmA and LnmZ exhibit substrate promiscuity, resulting in multiple LNM analogs from several shunt pathways; and (iii) the C-8 and C-4′ hydroxyl groups play important roles in the cytotoxicity of LNM analogs against different cancer cell lines, shedding light on the structure−activity relationships of the LNM scaffold and the LNM-type natural products in general. These studies set the stage for future biosynthetic pathway engineering and combinatorial biosynthesis of the LNM family of natural products for structure diversity and drug discovery.

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets., Covering: up to 2018 With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.

M.H.M. was supported by a Rubicon fellowship of the Netherlands Organization for Scientific Research (NWO;Rubicon 825.13.001). The work of R.K. was supported by the European Union’s Seventh Framework Programme(Joint Call OCEAN.2011–2: Marine microbial diversity—new insights into marine ecosystems functioning and its biotechnological potential) under the grant agreement no.287589 (Micro B3). M.C. was supported by a Biotechnology and Biological Sciences Research Council (BBSRC)studentship (BB/J014478/1). The GSC is supported by funding from the Natural Environment Research Council(UK), the National Institute for Energy Ethics and Society(NIEeS; UK), the Gordon and Betty Moore Foundation,the National Science Foundation (NSF; US) and the US Department of Energy. The Manchester Synthetic Biology Research Centre, SYNBIOCHEM, is supported by BBSRC/Engineering and Physical Sciences Research Council(EPSRC) grant BB/M017702/1, Medema, M.H., Kottmann, R., Yilmaz, P., Cummings, M., Biggins, J.B., Blin, K., De Bruijn, I., Chooi, Y.H., Claesen, J., Coates, R.C., Cruz-Morales, P., Duddela, S., Düsterhus, S., Edwards, D.J., Fewer, D.P., Garg, N., Geiger, C., Gomez-Escribano, J.P., Greule, A., Hadjithomas, M., Haines, A.S., Helfrich, E.J.N., Hillwig, M.L., Ishida, K., Jones, A.C., Jones, C.S., Jungmann, K., Kegler, C., Kim, H.U., Kötter, P., Krug, D., Masschelein, J., Melnik, A.V., Mantovani, S.M., Monroe, E.A., Moore, M., Moss, N., Nützmann, H.-W., Pan, G., Pati, A., Petras, D., Reen, F.J., Rosconi, F., Rui, Z., Tian, Z., Tobias, N.J., Tsunematsu, Y., Wiemann, P., Wyckoff, E., Yan, X., Yim, G., Yu, F., Xie, Y., Aigle, B., Apel, A.K., Balibar, C.J., Balskus, E.P., Barona-Gómez, F., Bechthold, A., Bode, H.B., Borriss, R., Brady, S.F., Brakhage, A.A., Caffrey, P., Cheng, Y.Q., Clardy, J., Cox, R.J., De Mot, R., Donadio, S., Donia, M.S., Van Der Donk, W.A., Dorrestein, P.C., Doyle, S., Driessen, A.J.M., Ehling-Schulz, M., Entian, K.-D., Fischbach, M.A., Gerwick, L., Gerwick, W.H., Gross, H., Gust, B., Hertweck, C., Höfte, M., Jensen, S.E., Ju, J., Katz, L., Kaysser, L., Klassen, J.L., Keller, N.P., Kormanec, J., Kuipers, O.P., Kuzuyama, T., Kyrpides, N.C., Kwon, H.-J., Lautru, S., Lavigne, R., Lee, C.Y., Linquan, B., Liu, X., Liu, W., Luzhetskyy, A., Mahmud, T., Mast, Y., Méndez, C., Metsä-Ketelä, M., Micklefield, J., Mitchell, D.A., Moore, B.S., Moreira, L.M., Müller, R., Neilan, B.A., Nett, M., Nielsen, J., O'Gara, F., Oikawa, H., Osbourn, A., Osburne, M.S., Ostash, B., Payne, S.M., Pernodet, J.-L., Petricek, M., Piel, J., Ploux, O., Raaijmakers, J.M., Salas, J.A., Schmitt, E.K., Scott, B., Seipke, R.F., Shen, B., Sherman, D.H., Sivonen, K., Smanski, M.J., Sosio, M., Stegmann, E., Süssmuth, R.D., Tahlan, K., Thomas, C.M., Tang, Y., Truman, A.W., Viaud, M., Walton, J.D., Walsh, C.T., Weber, T., Van Wezel, G.P., Wilkinson, B., Willey, J.M., Wohlleben, W., Wright, G.D., Ziemert, N., Zhang, C., Zotchev, S.B., Breitling, R., Takano, E., Glöckner, F.O.

A heterobimetallic complex, zinc titanium glycolate acetate hydrate (Zn2Ti3–GAH), tentatively formulated as Zn2Ti3(OCH2CH2O)4(OCH2CH2OH)5(CH3COO)3·2HOCH2CH2OH·H2O, was synthesized by a room-temperature homogeneous precipitation in ethylene glycol solution. Its chemical composition, crystal structure, morphology, growth mechanism and thermal behaviors were characterized in detail. The precipitated Zn2Ti3–GAH was of a highly crystalline monoclinic phase and porous microrod morphology. As the single source precursor (SSP), Zn2Ti3–GAH was transformed into different phases of zinc titanate via thermal decomposition. With the remaining shape of the microrods, cubic phases of Zn2Ti3O8 and rutile TiO2 (r-TiO2) supported hexagonal phases of ZnTiO3 (h-ZnTiO3) were obtained by calcination at 500 and 700 °C, respectively; while r-TiO2 supported Zn2TiO4 were yielded in the form of dispersed particles or chains at higher temperature (950 °C). Benefiting from the SSP route and the confinement in the specific microrod domains of precursors, the heterostructures of r-TiO2–ZnTiO3 and r-TiO2–Zn2TiO4 were formed during programmable calcination. The studies on photocatalysis by degrading methylene blue (MB) under ultraviolet (UV) irradiation indicated that the as-transformed zinc titanate exhibited enhanced activity. In particular, r-TiO2 supported h-ZnTiO3 displayed the photodegradation reaction rate constant of 0.00163 s−1, which was comparable to that of commercially available Degussa P25 TiO2. This probably related to the more effective charge separation in the r-TiO2–ZnTiO3 heterostructure packed in the microrods.

Wuyiencin is produced by Streptomyces ahygroscopicus var. wuyiensis CK-15 and is widely used as an antifungal agent in agriculture. Analysis of wuyiencin biosynthetic gene clusters reveals wysR, a member of the LAL-family of transcriptional regulatory genes. WysR consists of an Nterminal PAS domain and a LuxR family C-terminal helix-turn-helix motif. However, the roles of wysR in wuyiencin biosynthesis are largely unknown. In this study, we showed that inactivation of wysR resulted in the complete loss of wuyiencin production, which could be restored by complementation with a single copy of wysR. Furthermore, we successfully increased wuyiencin production to a significantly higher level by overexpression of wysR in S. wuyiensis CK-15. Quantitative real-time RT-PCR analysis showed that WysR regulates wuyiencin biosynthesis by modulating other putative regulatory genes. Thus, WysR was identified as an activator of wuyiencin biosynthesis, and overexpression of wysR gene proved to be an effective strategy for improving wuyiencin production.

Jadomycin production is under complex regulation in Streptomyces venezuelae. Here, another cluster-situated regulator, JadR*, was shown to negatively regulate jadomycin biosynthesis by binding to four upstream regions of jadY, jadR1, jadI and jadE in jad gene cluster respectively. The transcriptional levels of four target genes of JadR* increased significantly in ΔjadR*, confirming that these genes were directly repressed by JadR*. Jadomycin B (JdB) and its biosynthetic intermediates 2,3-dehydro-UWM6 (DHU), dehydrorabelomycin (DHR) and jadomycin A (JdA) modulated the DNA-binding activities of JadR* on the jadY promoter, with DHR giving the strongest dissociation effects. Direct interactions between JadR* and these ligands were further demonstrated by surface plasmon resonance, which showed that DHR has the highest affinity for JadR*. However, only DHU and DHR could induce the expression of jadY and jadR* in vivo. JadY is the FMN/FAD reductase supplying cofactors FMNH₂/FADH₂ for JadG, an oxygenase, that catalyses the conversion of DHR to JdA. Therefore, our results revealed that JadR* and early pathway intermediates, particularly DHR, regulate cofactor supply by a convincing case of a feed-forward mechanism. Such delicate regulation of expression of jadY could ensure a timely supply of cofactors FMNH₂/FADH₂ for jadomycin biosynthesis, and avoid unnecessary consumption of NAD(P)H.

A 980nm laser-driven antimicrobial photothermal therapy using poly(vinylpyrrolidone) -coated Prussian Blue nanoparticles (PVP/PB NPs) is demonstrated. This approach allows an efficient eradication of a virulent strain of Gram-negative Escherichia coli (E. coli) associated with urinary tract infection as well as for the ablation of antibiotic resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA) and extended spectrum β-lactamase (ESBL) E. coli. Interestingly the 980nm irradiation exhibits minimal effect on mammalian cells up to a PVP/PB NPs concentration of 50μgmL(-1), while at this concentration bacteria are completely eradicated. This feature is certainly very promising for the selective targeting of bacteria over mammalian cells.

The cyclic adenosine monophosphate (cAMP) receptor protein/fumarate and nitrate reductase regulatory protein (Crp/Fnr) family of transcriptional regulators are pleiotropic transcriptional regulators that control a broad range of cellular functions. Leinamycin (LNM) is a potent antitumor antibiotic produced by Streptomyces atroolivaceus S-140. We previously cloned and characterized the lnm biosynthetic gene cluster from S. atroolivaceus S-140. We here report inactivation of lnmO in S. atroolivaceus S-140 and overexpression of lnmO in the S. atroolivaceus S-140 wild-type and ∆lnmE mutant SB3033 to investigate its role in LNM biosynthesis. Bioinformatics analysis revealed LnmO as the only regulator within the lnm gene cluster, exhibiting high sequence similarity to known Crp/Fnr family regulators. The inactivation of lnmO in S. atroolivaceus S-140 completely abolished LNM production but caused no apparent morphological changes, supporting that LnmO is indispensable and specific to LNM biosynthesis. Overexpression of lnmO in S. atroolivaceus S-140 and SB3033 resulted in three- and fourfold increase in LNM and LNM E1 production, respectively, supporting that LnmO acts as a positive regulator. While all of the Crp/Fnr family regulators studied to date appeared to be pleiotropic, our results support LnmO as the first Crp/Fnr family regulator that is pathway-specific. LnmO joins the growing list of regulators that could be exploited to improve secondary metabolite production in Streptomyces. Engineered strains overproducing LNM and LNM E1 will facilitate further mechanistic studies and clinical evaluation of LNM and LNM E1 as novel anticancer drugs.

International audience; Perturbations in glucose homeostasis is critical for human health, as hyperglycemia (defining diabetes) leads to premature death caused by macrovascular and microvascular complications. However, the simple and accurate detection of glucose in the blood at low cost remains a challenging task, although it is of great importance for the diagnosis and therapy of diabetic patients. In this work, carbon quantum dots decorated with copper oxide nanostructures (CQDs/Cu2O) are prepared by a simple hydrothermal approach, and their potential for electrochemical non-enzymatic glucose sensing is evaluated. The proposed sensor exhibits excellent electrocatalytic activity towards glucose oxidation in alkaline solutions. The glucose sensor is characterized by a wide concentration range from 6 µM to 6 mM, a sensitivity of 2.9 ± 0.2 µA·µM−1·cm−2, and a detection limit of 6 µM at a signal-to-noise ratio S/N = 3. The sensors are successfully applied for glucose determination in human serum samples, demonstrating that the CQDs/Cu2O-based glucose sensor satisfies the requirements of complex sample detection with adapted potential for therapeutic diagnostics

Leinamycin (LNM) is biosynthesized by a hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide synthase (PKS). Characterization of LnmI revealed ketosynthase (KS)-acyl carrier protein (ACP)-KS domains at the NRPS-PKS interface. Inactivation of the KS domain or ACP domain in vivo abolished LNM production, and the ACP domain can be phosphopantetheinylated in vitro. The LnmI KS-ACP-KS architecture represents a new mechanism for functional crosstalk between NRPS and AT-less type I PKS in the biosynthesis of hybrid peptide-polyketide natural products.

The aim of the study was to test a tailored lifestyle intervention for helping obese primary care patients achieve weight loss and increase physical activity.We conducted a 24-month randomized clinical trial in Rhode Island. Primary care physicians identified obese, sedentary patients motivated to lose weight and increase their moderate to vigorous physical activity. These patients were randomized to 1 of 2 experimental groups: enhanced intervention (EI) or standard intervention (SI). Both groups received 3 face-to-face weight loss meetings. The enhanced intervention group also received telephone counseling calls, individually tailored print materials, and DVDs focused on diet and physical activity. Active intervention occurred in year 1 with a tapered maintenance phase in year 2.Two hundred eleven obese, sedentary patients were recruited from 24 primary care practices. Participants were 79% women and 16% minorities. They averaged 48.6 years of age, with a mean body mass index (BMI) of 37.8 kg/m(2), and 21.2 minutes/week of moderate to vigorous physical activity. Significantly more EI participants lost 5% of their baseline weight than SI participants (group by visit, P.001). The difference was significant during active treatment at 6 months (37.2% EI vs 12.9% SI) and 12 months (47.8% vs 11.6%), but was no longer significant during the maintenance phase at 18 months (31.4% vs 26.7%,) or 24 months (33.3% vs 24.6%). The EI group reported significantly more minutes of moderate to vigorous physical activity over time than the SI group (group by visit, P = 0.04). The differences in minutes per week at 6 months was 95.7 for the EI group vs 68.3 minutes for the SI group; at 12 months, it was 126.1 vs 73.7; at 18 months, 103.7 vs 63.7, and at 24 months, 101.3 vs 75.4. Similar trends were found for absolute weight loss and the percentage reaching national guidelines for physical activity.A home-based tailored lifestyle intervention in obese, sedentary primary care patients was effective in promoting weight loss and increasing moderate to vigorous physical activity, with the effects peaking at 12 months but waning at 24 months.

In this study, a new matrix based on a molybdenum disulfide-reduced graphene oxide hybrid (MoS2-rGO) was prepared and characterized. Modification of a glassy carbon electrode (GCE) with MoS2-rGO (MG) using drop casting allowed for the selective analysis of folic acid in the presence of a variety of interference species with a limit of detection of 10 nM, a linear range between 0.01 μM and 100 μM with a sensitivity of 14 µA µM−1. In addition, the analytical performance of the proposed sensor was successfully conducted for the determination of folic acid in human serum samples, making MG-GC electrodes promising interfaces for bio-electrochemical applications.

SummaryJadomycin B is a member of atypical angucycline antibiotics whose biosynthesis involves a unique ring opening C-C bond cleavage reaction. Here, we firmly identified JadG as the enzyme responsible for the B ring opening reaction in jadomycin biosynthesis. In vitro analysis of the JadG catalyzed reaction revealed that it requires FMNH2 or FADH2 as cofactors in the conversion of dehydrorabelomycin to jadomycin A. The cofactors could be supplied by either a cluster-situated flavin reductase JadY or the Escherichia coli Fre. JadY was characterized as a NAD(P)H-dependent FMN/FAD reductase, with FMN as the preferred substrate. Disruption mutant of jadY still produced jadomycin, indicating that the function of JadY could be substituted by other enzymes in the host. JadG represents the biochemically verified member of an enzyme class catalyzing an unprecedented C-C bond cleavage reaction.

SummaryThe Fat pathway controls both planar cell polarity (PCP) and organ growth [1, 2]. Fat signaling is regulated by the graded expression of the Fat ligand Dachsous (Ds) and the cadherin-domain kinase Four-jointed (Fj). The vectors of these gradients influence PCP [1], whereas their slope can influence growth [3, 4]. The Fj and Ds gradients direct the polarized membrane localization of the myosin Dachs, which is a crucial downstream component of Fat signaling [5–7]. Here we show that repolarization of Dachs by differential expression of Fj or Ds can propagate through the wing disc, which indicates that Fj and Ds gradients can be measured over long range. Through characterization of tagged genomic constructs, we show that Ds and Fat are themselves partially polarized along the endogenous Fj and Ds gradients, providing a mechanism for propagation of PCP within the Fat pathway. We also identify a biochemical mechanism that might contribute to this polarization by showing that Ds is subject to endoproteolytic cleavage and that the relative levels of Ds isoforms are modulated by Fat.

High quality thulium doped Lu1.6Sc0.4O3 mixed sesquioxide laser ceramics were fabricated using a solid-state reactive sintering method. Optical and spectroscopic properties of the ceramics were studied. A high transmittance almost identical to the theoretical value of the ceramics was reached at the lasing wavelength. A large Stark splitting of 920 cm−1 for the ground states 3H6 and 472 cm−1 for the first excited states 3F4 of Tm3+ were observed, resulting in a long wavelength emission band around 2.09 μm with low reabsorption losses at this wavelength. CW laser operation at 2.09 μm pumped by a 796 nm laser diode was achieved with an output power of 11 W and an optical-to-optical conversion efficiency of 28.9%, both of which are the highest values reported so far for lasing around 2.1 μm in Tm3+ doped mixed sesquioxide ceramics.

Tyrosine phosphorylation mediates multiple signal transduction pathways that play key roles in developmental processes and behavioral plasticity. The level of tyrosine phosphorylation is regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Extensive studies have investigated the roles of tyrosine kinases in memory formation. However, there were few studies on PTPs. To date, learning has been shown to be defective only for mouse knock-outs of PTPα, leukocyte common antigen-related, or PTPδ. A major limitation of these studies arises from their inability to distinguish an acute (biochemical) impairment of memory formation from a more chronic abnormality in neurodevelopment. From a behavioral screen for defective long-term memory, we foundchimutants to disrupt expression of the PTP10D protein tyrosine phosphatase gene. We show thatchimutants are normal for learning, early memory, and anesthesia-resistant memory, whereas long-term memory specifically is abolished. Significantly, induction of a heat shock-PTP10D+transgene before training fully rescues the memory defect ofchimutants, thereby demonstrating an acute role for PTP10D in behavioral plasticity. We show that PTP10D is widely expressed in the embryonic CNS and in the adult brain. Transgenic expression of upstream activating sequence-PTP10D+in mushroom bodies is sufficient to rescue the memory defect ofchimutants. Our data clearly demonstrate that signaling through PTP10D in mushroom bodies is critical for the formation of long-term memory.

The glutarimide-containing polyketides represent a fascinating class of natural products that exhibit a multitude of biological activities. We have recently cloned and sequenced the biosynthetic gene clusters for three members of the glutarimide-containing polyketides-iso-migrastatin (iso-MGS) from Streptomyces platensis NRRL 18993, lactimidomycin (LTM) from Streptomyces amphibiosporus ATCC 53964, and cycloheximide (CHX) from Streptomyces sp. YIM56141. Comparative analysis of the three clusters identified mgsA and chxA, from the mgs and chx gene clusters, respectively, that were predicted to encode the PimR-like Streptomyces antibiotic regulatory proteins (SARPs) but failed to reveal any regulatory gene from the ltm gene cluster. Overexpression of mgsA or chxA in S. platensis NRRL 18993, Streptomyces sp. YIM56141 or SB11024, and a recombinant strain of Streptomyces coelicolor M145 carrying the intact mgs gene cluster has no significant effect on iso-MGS or CHX production, suggesting that MgsA or ChxA regulation may not be rate-limiting for iso-MGS and CHX production in these producers. In contrast, overexpression of mgsA or chxA in S. amphibiosporus ATCC 53964 resulted in a significant increase in LTM production, with LTM titer reaching 106 mg/L, which is five-fold higher than that of the wild-type strain. These results support MgsA and ChxA as members of the SARP family of positive regulators for the iso-MGS and CHX biosynthetic machinery and demonstrate the feasibility to improve glutarimide-containing polyketide production in Streptomyces strains by exploiting common regulators.

An inorganic-organic hybrid semiconductor, ZnS/CHA (CHA = cyclohexylamine) nanocomposites was successfully synthesized via a solvothermal method using CHA as solvent, which yielded uniform and ultralong nanowires with widths of 100-1000 nm and lengths of 5-20 microm. Changing the reaction conditions could alter the morphology and optical properties of the nanocomposites. The periodic layer subnanometer structures were identified by high-resolution transmission electron microscopy (HR-TEM) images, with thickness of approximately 2 nm. The composites exhibited a very large blue-shift in their optical absorption edge as well as an exciton excitation band due to a strong quantum confinement effect caused by the internal subnanometer-scale structures. The pure hexagonal wurtzite ZnS nanowires were also obtained by extracting the ZnS/CHA nanocomposites with dimethyl formamide (DMF). In addition, the luminescent properties of exciton and defect-related transitions in different samples of ZnS/CHA were discussed in detail.