Drought at the global scale in the 2nd part of the 20th century (1963-2001)

The large impacts of drought on society, economy and environment urge for a thorough investigation. A good knowledge of past drought events is important for both understanding of the processes causing drought, as well as to provide reliability assessments for drought projections for the future. Preferably, the investigation of historic drought events should rely on observations. Unfortunately, for a global scale these detailed observations are often not available. Therefore, the outcome of global hydrological models (GHMs) and off-line land surface models (LSMs) is used to assess droughts. In this study we have investigated to what extent simulated gridded time series from these large-scale models capture historic hydrological drought events. Results of ten different models, both GHMs and LSMs, made available by the WATCH project, were compared. All models are run on a global 0.5 degree grid for the period 1963-2000 with the same meteorological forcing data (WATCH forcing data). To identify hydrological drought events, the monthly aggregated total runoff values were used. Different methods were developed to identify spatio-temporal drought characteristics. General drought characteristics for each grid cell, as for example the average drought duration, were compared. These characteristics show that when comparing absolute values the models give substantially different results, whereas relative values lead to more or less the same drought pattern. Next to the general drought characteristics, some documented major historical drought events (one for each continent) were selected and described in more detail. For each drought event, the simulated drought clusters (spatial events) and their characteristics are given for one month during the event. It can be concluded that most major drought events are captured by all models. However, the spatial extent of the drought events differ substantially between the models. In general the models show a fast reaction to rainfall and therefore also capture drought events caused by large rainfall anomalies. More research is still needed, since here we only looked at a few selected number of documented drought events spread over the globe. To assess more in detail if these large-scale models are able to capture drought, additional quantitative analyses are needed together with a more elaborated comparison against observed drought events

Biosynthetic and Synthetic Strategies for Assembling Capuramycin-Type Antituberculosis Antibiotics

Mycobacterium tuberculosis (Mtb) has recently surpassed HIV/AIDS as the leading cause of death by a single infectious agent. The standard therapeutic regimen against tuberculosis (TB) remains a long, expensive process involving a multidrug regimen, and the prominence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains continues to impede treatment success. An underexplored class of natural products—the capuramycin-type nucleoside antibiotics—have been shown to have potent anti-TB activity by inhibiting bacterial translocase I, a ubiquitous and essential enzyme that functions in peptidoglycan biosynthesis. The present review discusses current literature concerning the biosynthesis and chemical synthesis of capuramycin and analogs, seeking to highlight the potential of the capuramycin scaffold as a favorable anti-TB therapeutic that warrants further development

Self-Resistance During Muraymycin Biosynthesis: A Complementary Nucleotidyltransferase and Phosphotransferase with Identical Modification Sites and Distinct Temporal Order

Muraymycins are antibacterial natural products from Streptomyces spp. that inhibit translocase I (MraY), which is involved in cell wall biosynthesis. Structurally, muraymycins consist of a 5′-C-glycyluridine (GlyU) appended to a 5″-amino-5″-deoxyribose (ADR), forming a disaccharide core that is found in several peptidyl nucleoside inhibitors of MraY. For muraymycins, the GlyU-ADR disaccharide is further modified with an aminopropyl-linked peptide to generate the simplest structures, annotated as the muraymycin D series. Two enzymes encoded in the muraymycin biosynthetic gene cluster, Mur29 and Mur28, were functionally assigned in vitro as a Mg·ATP-dependent nucleotidyltransferase and a Mg·ATP-dependent phosphotransferase, respectively, both modifying the 3″-OH of the disaccharide. Biochemical characterization revealed that both enzymes can utilize several nucleotide donors as cosubstrates and the acceptor substrate muraymycin also behaves as an inhibitor. Single-substrate kinetic analyses revealed that Mur28 preferentially phosphorylates a synthetic GlyU-ADR disaccharide, a hypothetical biosynthetic precursor of muraymycins, while Mur29 preferentially adenylates the D series of muraymycins. The adenylated or phosphorylated products have significantly reduced (170-fold and 51-fold, respectively) MraY inhibitory activities and reduced antibacterial activities, compared with the respective unmodified muraymycins. The results are consistent with Mur29-catalyzed adenylation and Mur28-catalyzed phosphorylation serving as complementary self-resistance mechanisms, with a distinct temporal order during muraymycin biosynthesis

Global multimodel analysis of drought in runoff for the second half of the twentieth century

During the past decades large-scale models have been developed to simulate global and continental terrestrial water cycles. It is an open question whether these models are suitable to capture hydrological drought, in terms of runoff, on global scale. A multi-model ensemble analysis was carried out to evaluate if ten of such large-scale models agree on major drought events during the second half of the 20th century. Time series of monthly precipitation, monthly total runoff from ten global hydrological models, and their ensemble median have been used to identify drought. Temporal development of area in drought for various regions across the globe was investigated. Model spread was largest in regions with low runoff and smallest in regions with high runoff. In vast regions, correlation between runoff drought derived from the models and meteorological drought was found to be low. This indicated that models add information to the signal derived from precipitation and that runoff drought cannot directly be determined from precipitation data alone in global drought analyses with a constant aggregation period. However, duration and spatial extent of major drought events differed between models. Some models showed a fast runoff response to rainfall, which led to deviations from reported drought events in slowly responding hydrological systems. By using an ensemble of models, this fast runoff response was partly overcome and delay in drought propagating from meteorological drought to drought in runoff was included. Finally, an ensemble of models also allows to consider uncertainty associated with individual model structures

Structure and Function of a Dual Reductase–Dehydratase Enzyme System Involved in p-Terphenyl Biosynthesis

We report the identification of the ter gene cluster responsible for the formation of the p-terphenyl derivatives terfestatins B and C and echoside B from the Appalachian Streptomyces strain RM-5-8. We characterize the function of TerB/C, catalysts that work together as a dual enzyme system in the biosynthesis of natural terphenyls. TerB acts as a reductase and TerC as a dehydratase to enable the conversion of polyporic acid to a terphenyl triol intermediate. X-ray crystallography of the apo and substrate-bound forms for both enzymes provides additional mechanistic insights. Validation of the TerC structural model via mutagenesis highlights a critical role of arginine 143 and aspartate 173 in catalysis. Cumulatively, this work highlights a set of enzymes acting in harmony to control and direct reactive intermediates and advances fundamental understanding of the previously unresolved early steps in terphenyl biosynthesis

Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated \u3cem\u3eStreptomyces\u3c/em\u3e

We report the isolation and characterization of three new nybomycins (nybomycins B–D, 1–3) and six known compounds (nybomycin, 4; deoxynyboquinone, 5; α-rubromycin, 6; β-rubromycin, 7; γ-rubromycin, 8; and [2α(1E,3E),4β]-2-(1,3-pentadienyl)-4-piperidinol, 9) from the Rock Creek (McCreary County, KY) underground coal mine acid reclamation site isolate Streptomyces sp. AD-3-6. Nybomycin D (3) and deoxynyboquinone (5) displayed moderate (3) to potent (5) cancer cell line cytotoxicity and displayed weak to moderate anti-Gram-(+) bacterial activity, whereas rubromycins 6–8 displayed little to no cancer cell line cytotoxicity but moderate to potent anti-Gram-(+) bacterial and antifungal activity. Assessment of the impact of 3 or 5 cancer cell line treatment on 4E-BP1 phosphorylation, a predictive marker of ROS-mediated control of cap-dependent translation, also revealed deoxynyboquinone (5)-mediated downstream inhibition of 4E-BP1p. Evaluation of 1–9 in a recently established axolotl embryo tail regeneration assay also highlighted the prototypical telomerase inhibitor γ-rubromycin (8) as a new inhibitor of tail regeneration. Cumulatively, this work highlights an alternative nybomycin production strain, a small set of new nybomycin metabolites, and previously unknown functions of rubromycins (antifungal activity and inhibition of tail regeneration) and also provides a basis for revision of the previously proposed nybomycin biosynthetic pathway