Chemical Evolution of a Bacterial Proteome

We have changed the amino acid set of the genetic code of Escherichia coli by evolving cultures capable of growing on the synthetic noncanonical amino acid L ‐β‐(thieno[3,2‐b]pyrrolyl)alanine ([3,2]Tpa) as a sole surrogate for the canonical amino acid L ‐tryptophan (Trp). A long‐term cultivation experiment in defined synthetic media resulted in the evolution of cells capable of surviving Trp→[3,2]Tpa substitutions in their proteomes in response to the 20 899 TGG codons of the E. coli W3110 genome. These evolved bacteria with new‐to‐nature amino acid composition showed robust growth in the complete absence of Trp. Our experimental results illustrate an approach for the evolution of synthetic cells with alternative biochemical building blocks.     

Structure Elucidation and Activity of Kolossin A,the D‐/L‐Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase

The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D ‐/ L ‐peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness.     

Reductive Insertion of Elemental Chalcogens into Boron–Boron Multiple Bonds

The syntheses of sulfur‐ and selenium‐bridged cyclic compounds containing boron stabilized by N‐heterocyclic carbenes (NHCs) have been achieved by the reductive insertion of elemental chalcogens into boron–boron multiple bonds. The three pairs of bonding electrons between the boron atoms in the triply bonded diboryne enabled six‐electron reduction reactions, resulting in the formation of [2.2.1]‐bicyclic systems wherein bridgehead boron atoms are spanned by three chalcogen bridges. A similar reaction using a diborene (boron–boron double bond) resulted in the reductive transfer of both pairs of bonding electrons to three sulfur atoms, yielding a NHC‐stabilized trisulfidodiborolane. The demonstration of these six‐ and four‐electron reductions lends support to the presence of three and two pairs of bonding electrons between the boron atoms of the diboryne and diborene, respectively, a fact that may be useful in future discussions on bond order.     

Electronic Olfactory Sensor Based on A. mellifera Odorant‐Binding Protein 14 on a Reduced Graphene Oxide Field‐Effect Transistor

An olfactory biosensor based on a reduced graphene oxide (rGO) field‐effect transistor (FET), functionalized by the odorant‐binding protein 14 (OBP14) from the honey bee (Apis mellifera) has been designed for the in situ and real‐time monitoring of a broad spectrum of odorants in aqueous solutions known to be attractants for bees. The electrical measurements of the binding of all tested odorants are shown to follow the Langmuir model for ligand–receptor interactions. The results demonstrate that OBP14 is able to bind odorants even after immobilization on rGO and can discriminate between ligands binding within a range of dissociation constants from K_d=4 μM to K_d=3.3 mM . The strongest ligands, such as homovanillic acid, eugenol, and methyl vanillate all contain a hydroxy group which is apparently important for the strong interaction with the protein.     

Production of the Bengamide Class of Marine Natural Products in Myxobacteria: Biosynthesis and Structure–Activity Relationships

The bengamides, sponge‐derived natural products that have been characterized as inhibitors of methionine aminopeptidases (MetAPs), have been intensively investigated as anticancer compounds. We embarked on a multidisciplinary project to supply bengamides by fermentation of the terrestrial myxobacterium M. virescens, decipher their biosynthesis, and optimize their properties as drug leads. The characterization of the biosynthetic pathway revealed that bacterial resistance to bengamides is conferred by Leu 154 of the myxobacterial MetAP protein, and enabled transfer of the entire gene cluster into the more suitable production host M. xanthus DK1622. A combination of semisynthesis of microbially derived bengamides and total synthesis resulted in an optimized derivative that combined high cellular potency in the nanomolar range with high metabolic stability, which translated to an improved half‐life in mice and antitumor efficacy in a melanoma mouse model.     

Energy Scaling of Compressed Elastic Films –Three-Dimensional Elasticity¶and Reduced Theories

We derive an optimal scaling law for the energy of thin elastic films under isotropic compression, starting from three-dimensional nonlinear elasticity. As a consequence we show that any deformation with optimal energy scaling must exhibit fine-scale oscillations along the boundary, which coarsen in the interior. This agrees with experimental observations of folds which refine as they approach the boundary. We show that both for three-dimensional elasticity and for the geometrically nonlinear Föppl-von Kármán plate theory the energy of a compressed film scales quadratically in the film thickness. This is intermediate between the linear scaling of membrane theories which describe film stretching, and the cubic scaling of bending theories which describe unstretched plates, and indicates that the regime we are probing is characterized by the interplay of stretching and bending energies. Blistering of compressed thin films has previously been analyzed using the Föppl-von Kármán theory of plates linearized in the in-plane displacements, or with the scalar eikonal functional where in-plane displacements are completely neglected. The predictions of the linearized plate theory agree with our result, but the scalar approximation yields a different scaling.     

PopGen: population-based recruitment of patients and controls for the analysis of complex genotype-phenotype relationships

OBJECTIVE: Patient samples used for mapping complex human disease genes are unlikely to be representative of the phenotype spectrum of the respective population as a whole. On the other hand, most ongoing prospective studies are probably too small for evaluating polygenic disease markers. DESIGN: Precise estimates of population-specific genotypic risks can be obtained efficiently through the complete ascertainment of patients in a geographically confined area. The PopGen project uses the most northern part of Germany as a target region for such a pursuit. RESULTS: PopGen currently pursues recruitment, sampling and processing activities in close collaboration with a multitude of clinical partners, covering cardiovascular, neuropsychiatric and environmental diseases. CONCLUSION: PopGen has successfully established itself as a large-scale genetic epidemiological project of international recognition.     

Modeling the dynamic behavior of shape memory alloys

The paper studies the single degree of freedom vibration of a rigid mass suspended by a thin-walled shape memory alloy tube under torsional loading. The behavior is analyzed for the cases of quasiplasticity (low temperatures) and pseudoelasticity (high temperatures) on the basis of an improved version of the Müller–Achenbach model. To illustrate the strong hysteresis-induced damping capacity and the non-linear vibration characteristics, both, free and forced vibrations are considered in the first part of the paper. This is done on the basis of an isothermal version of the model, while the second part of the paper focuses on the effect of non-constant temperature caused by the rate-dependent release and absorption of latent heats.     

Dichotomy Spectrum for Nonautonomous Differential Equations

For nonautonomous linear differential equations x=A(t) x with locally integrable A: RR ^N×N the so-called dichotomy spectrum is investigated in this paper. As the closely related dichotomy spectrum for skew product flows with compact base (Sacker–Sell spectrum) our dichotomy spectrum for nonautonomous differential equations consists of at most N closed intervals, which in contrast to the Sacker–Sell spectrum may be unbounded. In the constant coefficients case these intervals reduce to the real parts of the eigenvalues of A. In any case the spectral intervals are associated with spectral manifolds comprising solutions with a common exponential growth rate. The main result of this paper is a spectral theorem which describes all possible forms of the dichotomy spectrum.