Editors' Choice

Science  11 Sep 2009:
Vol. 325, Issue 5946, pp. 1320
  1. Biotechnology

    Verkehrsknotenpunkt in Miniature

    1. Gilbert Chin
    CREDIT: © CARO/ALAMY

    Engineering microbes so that they produce desired molecules, such as the isoprenoid precursor mevalonic acid, can have the unhealthy side effect of rerouting the host's metabolism into a suboptimal configuration. Heterologous enzymes, if expressed at high levels, may rob the cell of essential metabolites or, conversely, may introduce toxic intermediates. One conceptual way around this problem would be to centralize the synthetic machinery, reducing the transit times of intermediates as they travel from one enzyme to the next, increasing local substrate concentrations, and decreasing exposure to the elements.

    In this vein, Dueber et al. have developed a modular system for constructing intracellular chemical factories. They fabricated joints by adding one of three well-characterized protein-protein interaction motifs—a GTPase binding domain, a Src homology domain, or a PDZ domain—to the N terminus of the downstream biosynthetic enzyme and the corresponding peptide ligand to the C terminus of the upstream enzyme. Varying the number of peptide ligands added and, independently, the number of peptide-binding domains attached generated a range of enhanced titers over that observed when uncatenated enzymes were used; one such combination yielded 5 mM mevalonate, an increase of almost two orders of magnitude. The advantage of building a self-contained enzyme complex, akin to the fatty acid synthases, is that the orthogonal production of chemicals imposes a tolerable cost on the host organism.

    Nat. Biotechnol. 27, 753 (2009).

  2. Microbiology

    Lying Dangerously Dormant

    1. Caroline Ash
    CREDIT: JUPITERIMAGES

    It was Louis Pasteur who first thought earthworms might play a part in aiding the persistence of anthrax in the soil. He did not follow up on this hunch, but observations on the sporadic occurrence of anthrax spores, coupled with the virus-infested nature of Bacillus anthracis and its close relatives, suggested to Schuch and Fischetti that this dangerous pathogen may do more in the soil than simply lie in wait, encased in a resistant coat. In a set of extensive analyses, B. anthracis was found to harbor not only its own distinctive virulence plasmids but also to act as host for several lysogenic bacteriophages.

    Lysogeny was found to alter the capacity of the bacterium to sporulate, to form biofilm exopolysaccharide, to reproduce vegetatively, and to colonize earthworm guts. Phage-encoded sigma factors transcriptionally activated bacterial loci to switch on these phenotypes, enabling B. anthracis and its cousins to live in the soil in a variety of modes, and not just as dormant spores.

    PLoS ONE 4, e6532 (2009).

  3. Climate Science

    Leafing Through Time

    1. Brooks Hanson

    Climate changes in Earth's history can inform our understanding of anthropogenic greenhouse gas forcing, but the resolution in the rock record for most events spans much longer periods (thousands to millions of years) than the rapid changes occurring today. For example, much of the Mesozoic (from about 250 to 65 million years ago) was warmer than today, and atmospheric CO2 levels then were generally higher, but resolving individual events during this time requires developing detailed proxies for both CO2 levels and paleoclimate and then correlating these different records in time. Retallack has attempted such an accounting for the past 300 million years, using the stomata of fossil Ginkgo leaves to infer past atmospheric CO2 levels (plants have fewer stomata when CO2 levels are high) and also measuring the occurrence and depth of carbonate nodules, which reflect precipitation and temperature, in more than 3700 paleosols in the western United States. In all, 40 noticeably wet excursions are indicated in the paleosol record, and many of these can be correlated, albeit with some uncertainties, with the inferred CO2 record (though the records don't fully overlap). With the caveat that there are assumptions and extrapolations in many steps of such an analysis, the results suggest that Mesozoic warmth included numerous extreme warm-wet excursions associated with extremely high CO2 levels.

    Geol. Soc. Am. Bull. 121, 1441 (2009)

  4. Chemistry

    Acid-Driven Delivery

    1. Phil Szuromi

    Rotaxane molecules consist of a macrocycle that can move along a linear threader. This movement can be constrained by creating docking sites along the threader, and the strength of these docking interactions in some cases can be controlled by pH. One concept for exploiting these molecular states is to create mechanized nanoparticles for pH-dependent release of trapped molecules. Angelos et al. prepared mesoporous silica nanoparticles using a template to create pores. The pore surfaces were derivatized with amine groups, which hold the threaders. On addition of large cucurbit[6]uril macrocycles and dye molecules to a particle dispersion near neutral pH, the macrocycles migrate to the particle surface and trap the dye in the pores. Raising or lowering the pH displaces the macrocycles and releases the dye, much like opening a valve. Unlike previous examples that only released the macrocycles at high pH, this system would operate at conditions useful for drug delivery—blood is near neutral pH, whereas lysosomal compartments are acidic.

    J. Am. Chem. Soc. 131, 10.1021/ja9010157 (2009).

  5. Chemistry

    A Distinct Take on Flex Fuel

    1. Jake Yeston
    CREDIT: TOMINAKA ET AL., ENERGY ENVIRON. SCI. 2, 10.1039/B915389F (2009)

    Technological miniaturization is rapidly reducing the macroscopic surface footprints needed for applications ranging from electronic circuits to chemical reactors. In this landscape, concomitant miniaturization of power sources such as batteries and fuel cells would be helpful to render chip systems self-sufficient, eliminating the need for connections to bulky external sources. Tominaka et al. present progress toward development of an efficient fuel cell roughly the size of a postage stamp, fabricated on flexible plastic to reduce the cost and brittleness associated with a silicon-based prototype. The device was prepared through a combination of hot embossing, photolithography, and electrodeposition, and operated with methanol fuel and ambient oxygen. The authors propose to improve the observed low power density by increasing the relative surface areas of the catalysts.

    Energy Environ. Sci. 2, 10.1039/b915389f (2009).

  6. Climate Science

    Believable Fingerprints

    1. H. Jesse Smith

    Detection and attribution studies of climate change compare climate model output to observed variations of some climate parameter, such as temperature or rainfall, to see if the “fingerprint” of the changes represented by the model matches that of the measured parameter, and thus whether the climate changes can be attributed to a specific cause. Agreement across multiple models suggests that the results are more believable and less prone to distortion by the shortcomings of any particular model. Santer et al. used 22 climate models to investigate changes in the water vapor content over the oceans of the world. Water vapor significantly influences climate in many ways, acting as the largest single source of radiative forcing and as a key component in the process of hurricane formation. The authors found that recent changes in water vapor are robustly linked to anthropogenic forcing, and that the success of a model's ability to reproduce water vapor changes is not linked to its success at representing other climate variables. That means the “one model–one vote” method of predicting climate change may not always be appropriate, even though it turned out that way in this study.

    Proc. Natl. Acad. Sci. U.S.A. 106, 10.1073/pnas.0901736106 (2009).

  7. Cancer

    Green Surgery

    1. Barbara R. Jasny

    One aspect of medicine that has remained largely unperturbed by high-tech bells and whistles is the need for surgeons to distinguish between tissue to be removed and tissue to leave behind. Kishimoto et al. have demonstrated the use of a viral vector that targets tumor cells specifically, not to kill them directly, but to demarcate cancerous tissue clearly. They started with a designed adenovirus, OBP-401, which can replicate only in cells that contain an active telomerase, as in malignant tissue. This virus also contains a gene for green fluorescent protein (GFP). In a proof-of-principle study, peritoneal tumors were induced in nude mice by injecting human cancer cells containing red fluorescent protein (RFP). Twelve days later, disseminated nodules had formed, and intraperitoneal injection of the virus and examination 5 days later revealed co-localization of red and green fluorescent signals. In a similar mouse model for pleural dissemination using unlabeled human lung cancer cells, nodules that would not have been detected by eye were clearly visualized via GFP. Although other tumor-imaging approaches are available, cancer-specific labeling could add value to the idea of virus-aided, fluorescence-guided surgery.

    Proc. Natl. Acad. Sci. U.S.A. 106, 14514 (2009).