Fr Francium

Wiley-VCH, Weinheim 2010, XXI+335 pp., hardcover € 99.00.—ISBN 978-3-527-32541-2

The inside cover picture shows the molecular structure of a DAG lactone derivative on top of the inner leaflet of a DMPC bilayer. The confocal microscopy image illustrates DAG-lactone-stimulated membrane localization of PKCδ-ECFP in living cells, while the space-filling model shows the surface of the C1B domain of PKCδ, the target of the lactone. For more information, see the paper by V. E. Marquez, S. Corbalan-Garcia, R. Jelinek et al. on p. 2003 ff.

The cover picture shows the enzyme–inhibitor complex of a bacterial fucosidase derived from human microbiota. Fucose is implicated in many diseases, notably cancer and human fucosidosis, consequently there is evolving interest in the inhibition and manipulation of enzymes involved in fucose processing. 3D structural analysis complemented by kinetics and isothermal titration calorimetry paint a portrait of fucosidase inhibitor binding in which pH effects within the active centre (red) modify binding properties. Manipulation of “aglycon-mimicking” chemistries and inhibitor pKa values are likely routes to optimal fucosidase inhibition in the context of cellular and mechanistic probes and potential therapeutic agents. For more information see the communication by G. Davies et al. on p. 1971 ff. Background photo of B. thetaiotaomicron adapted from L. Gross, PLoS Biol.2007, 5, e199, as permitted under the Creative Commons Attribution License Agreement.

Gingerol derivatives are bioactive compounds isolated from the rhizome of ginger. They possess various beneficial activities, such as anticancer and hepatoprotective activities, and are therefore attractive targets of bioengineering. However, the microbial production of gingerol derivatives has not yet been established, primarily because the biosynthetic pathway of gingerol is unknown. Here, we report the production of several dehydrogingerdione (a gingerol derivative) analogues from a recombinant Escherichia coli strain that has an “artificial” biosynthesis pathway for dehydrogingerdione that was not based on the original biosynthesis pathway of gingerol derivatives in plants. The system consists of a 4-coumarate:CoA ligase from Lithospermum erythrorhizon, a fatty acid CoA ligase from Oryza sativa, a β-oxidation system from Saccharomyces cerevisiae, and a curcuminoid synthase from O. sativa. To our knowledge, this is the first report of the microbial production of a plant metabolite the biosynthetic pathway of which has not yet been identified.Route ginger: Dehydrogingerdione analogues were produced by a recombinant E. coli strain that has an “artificial” biosynthesis pathway for dehydrogingerdione that is not based on the original biosynthesis pathway of gingerol derivatives in plants. At least theoretically, more than 100 dehydrogingerdione analogues could be produced by this system.

An oriented glyco-capturing macroligand was synthesized by site-specific immobilization of an O-cyanate chain-end-functionalized boronic acid containing polymer (boropolymer) onto an amine surface. The O-cyanate chain-end-functionalized boropolymer was synthesized by arylamine-initiated cyanoxyl-mediated free-radical polymerization in a one-pot fashion. The chain-end O-cyanate was confirmed by 13C NMR spectroscopy. The specific carbohydrate-binding capacity of the boropolymer was evaluated by an alizarin red S assay. Oriented and covalent immobilization of the O-cyanate chain-end-functionalized boropolymer onto the amine-modified solid surfaces and its specific glyco-capturing capacity were confirmed by the quartz crystal microbalance (QCM) and atomic force microscopy (AFM) techniques. The oriented multivalent glyco-capturing ligand can be used for efficient carbohydrate and glycoconjugate purification and identification, and thus is expected to constitute a core strategy of glycomics and glycoproteomics and carbohydrate-sensing applications.Sugar-capturing polymers: An oriented glyco-capturing macroligand was synthesized by site-specific immobilization of an O-cyanate chain-end-functionalized boronic acid containing polymer (boropolymer) onto an amine surface. Oriented and covalent immobilization of the O-cyanate chain-end-functionalized boropolymer onto amine-modified solid surfaces and its specific glyco-capturing capacity were confirmed by QCM and AFM.

In Arabidopsis thaliana cell cultures, the peptaibol alamethicin induced a form of active cell death that was associated with cell shrinkage and DNA fragmentation. The transfer of mature A. thaliana plants from a peptide-free medium to a medium containing a moderate concentration of alamethicin caused the development of lesions in leaves after a few days. These lesions were characterized by cell death, deposition of callose, production of autofluorescent phenolic compounds, and transcription of defense genes, just like in the hypersensitive response to a pathogen attack. The induction of defense-like responses in Arabidopsis by other membrane-disrupting peptides was also evaluated. The peptides selected for comparison included the natural antimicrobial melittin and the peptaibol ampullosporin A, as well as synthetic analogues of the peptaibols cervinin and trichogin. The response amplitude in A. thaliana increased with the peptaibol's ability to permeabilize biological membranes through a pore-forming mechanism and was strongly associated with their content in the helicogenic α-aminoisobutyric acid residue.Pore defense: Alamethicin strongly induces a hypersensitive-like local response and systemic lesions in Arabidopsis thaliana. The amplitude of the defense response is related to the presence of the helicogenic α-aminoisobutyric acid residues (U) in the alamethicin sequence and to the ability of this peptaibol to form pores in plasma membranes.

Nature constructs intricate complexes containing numerous binding partners in order to direct a variety of cellular processes. Researchers have taken a cue from these events to develop synthetic molecules that can nucleate natural and unnatural interactions for a diverse set of applications. These molecules can be designed to drive protein dimerization or to modulate the interactions between proteins, lipids, DNA, or RNA and thereby alter cellular pathways. A variety of components within the cellular machinery can be recruited with or replaced by synthetic compounds. Directing the formation of multicomponent complexes with new synthetic molecules can allow unprecedented control over the cellular machinery.Directing the formation of macromolecular complexes offers important opportunities for understanding and engineering cellular fate and function. Small synthetic components can be used to nucleate the formation of desired cellular machines. A great deal of control over cellular processes and more could be available by applying this concept to couple orthogonal scaffolds to elicit desired outcomes.

Ferritin encapsulation inside lipid vesicles reveals the spontaneous formation of protein-rich vesicles. The solute distribution inside the vesicles follows a power law. The important conclusion for origins-of-life scenarios is that the dynamics of membrane closure allow the accumulation of solutes inside primitive cells, thus providing an explanation for the origins of early functional cells.