Heterologous Expression and Engineering Studies of Labyrinthopeptins, Class III Lantibiotics from Actinomadura namibiensis

SummaryLabyrinthopeptins are class III lantibiotics produced by the actinomycete Actinomadura namibiensis. The most characteristic structural feature is the posttranslationally installed triamino triacid labionin with a quaternary α-carbon. In addition to the unique structure, labyrinthopeptin A2 possess remarkable antiviral and antiallodynic biological activities. To harness the substrate tolerance of the biosynthetic machinery, we developed an efficient system for the generation of labyrinthopeptin analogs. Streptomyces lividans was used as a heterologous host since the natural producer Actinomadura namibiensis remained genetically intractable. Generation of a library of 39 mutants allowed identification of variable and invariable regions in the labyrinthopeptin structures. Additional data on the flexibility of the biosynthetic machinery were provided by in vitro experiments. This study is detailed investigation on the potential to generate analogs of class III lantibiotics by genetic engineering

Optimization of Artificial Siderophores as 68Ga-Complexed PET Tracers for in Vivo Imaging of Bacterial Infections

The diagnosis of bacterial infections at deep body sites benefits from noninvasive imaging of molecular probes that can be traced by positron emission tomography (PET). We specifically labeled bacteria by targeting their iron transport system with artificial siderophores. The cyclen-based probes contain different binding sites for iron and the PET nuclide gallium-68. A panel of 11 siderophores with different iron coordination numbers and geometries was synthesized in up to 8 steps, and candidates with the best siderophore potential were selected by a growth recovery assay. The probes [68Ga]7 and [68Ga]15 were found to be suitable for PET imaging based on their radiochemical yield, radiochemical purity, and complex stability in vitro and in vivo. Both showed significant uptake in mice infected with Escherichia coli and were able to discern infection from lipopolysaccharide-triggered, sterile inflammation. The study qualifies cyclen-based artificial siderophores as readily accessible scaffolds for the in vivo imaging of bacteria

Mechanism of periodic height variations along self-aligned VLS-grown planar nanostructures

In this study we report in-plane nanotracks produced by molecular-beam-epitaxy (MBE) exhibiting lateral self-assembly and unusual periodic and out-of-phase height variations across their growth axes. The nanotracks are synthesized using bismuth segregation on the GaAsBi epitaxial surface, which results in metallic liquid droplets capable of catalyzing GaAsBi nanotrack growth via the vapor–liquid–solid (VLS) mechanism. A detailed examination of the nanotrack morphologies is carried out employing a combination of scanning electron and atomic force microscopy and, based on the findings, a geometric model of nanotrack growth during MBE is developed. Our results indicate diffusion and shadowing effects play significant roles in defining the interesting nanotrack shape. The unique periodicity of our lateral nanotracks originates from a rotating nucleation “hot spot” at the edge of the liquid–solid interface, a feature caused by the relative periodic circling of the non-normal ion beam flux incident on the sample surface, inside the MBE chamber. We point out that such a concept is divergent from current models of crawling mode growth kinetics and conclude that these effects may be utilized in the design and assembly of planar nanostructures with controlled non-monotonous structure

Study of the temperature distribution in Si nanowires under microscopic laser beam excitation

The use of laser beams as excitation sources for the characterization of semiconductor nanowires (NWs) is largely extended. Raman spectroscopy and photoluminescence (PL) are currently applied to the study of NWs. However, NWs are systems with poor thermal conductivity and poor heat dissipation, which result in unintentional heating under the excitation with a focused laser beam with microscopic size, as those usually used in microRaman and microPL experiments. On the other hand, the NWs have subwavelength diameter, which changes the optical absorption with respect to the absorption in bulk materials. Furthermore, the NW diameter is smaller than the laser beam spot, which means that the optical power absorbed by the NW depends on its position inside the laser beam spot. A detailed analysis of the interaction between a microscopic focused laser beam and semiconductor NWs is necessary for the understanding of the experiments involving laser beam excitation of NWs. We present in this work a numerical analysis of the thermal transport in Si NWs, where the heat source is the laser energy locally absorbed by the NW. This analysis takes account of the optical absorption, the thermal conductivity, the dimensions, diameter and length of the NWs, and the immersion medium. Both free standing and heat-sunk NWs are considered. Also, the temperature distribution in ensembles of NWs is discussed. This analysis intends to constitute a tool for the understanding of the thermal phenomena induced by laser beams in semiconductor NWs

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data

MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms’ role in ecology and human health

Olfaction, taste and chemoreception: scientific evidence replaces "Essays in biopoetry".

Giovanni Appendino, Mark Brönstrup and Julia Kubanek introduce the Natural Product Reports themed issue on ‘Olfaction, taste and chemoreception’.</p

Target identification by image analysis

Each biologically active compound induces phenotypic changes in target cells that are characteristic for its mode of action. These phenotypic alterations can be directly observed under the microscope or made visible by labelling structural elements or selected proteins of the cells with dyes. A comparison of the cellular phenotype induced by a compound of interest with the phenotypes of reference compounds with known cellular targets allows predicting its mode of action. While this approach has been successfully applied to the characterization of natural products based on a visual inspection of images, recent studies used automated microscopy and analysis software to increase speed and to reduce subjective interpretation. In this review, we give a general outline of the workflow for manual and automated image analysis, and we highlight natural products whose bacterial and eucaryotic targets could be identified through such approaches

Antiviral drug discovery: broad-spectrum drugs from nature.

Covering: up to April 2014. The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with scepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has re-bloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, with particular focus on natural products as promising starting points for antiviral lead development

Modeling the dielectric function of degenerately doped ZnO Al thin films grown by ALD using physical parameters

Transparent conductive thin films are a key building block of modern optoelectronic devices. A promising alternative to expensive indium containing oxides is aluminum doped zinc oxide AZO . By correlating spectroscopic ellipsometry and photoluminescence, we analyzed the contributions of different optical transitions in AZO grown by atomic layer deposition to a model dielectric function MDF over a wide range of photon energies. The derived MDF reflects the effects of the actual band structure and therefore describes the optical properties very accurately. The presented MDF is solely based on physically meaningful parameters in contrast to empirical models like e.g. the widely used Sellmeier equation, but nevertheless real and imaginary parts are expressed as closed form expressions. We analyzed the influence of the position of the Fermi energy and the Fermi edge singularity to the different parts of the MDF. This information is relevant for design and simulation of optoelectronic devices and can be determined by analyzing the results from spectroscopic ellipsometr