Explorations of catalytic domains in non-ribosomal peptide synthetase enzymology

Covering up to the end of 2011Many pharmaceuticals on the market today belong to a large class of natural products called nonribosomal peptides (NRPs). Originating from bacteria and fungi, these peptide-based natural products consist not only of the 20 canonical l-amino acids, but also non-proteinogenic amino acids, heterocyclic rings, sugars, and fatty acids, generating tremendous chemical diversity. As a result, these secondary metabolites exhibit a broad array of bioactivity, ranging from antimicrobial to anticancer. The biosynthesis of these complex compounds is carried out by large multimodular megaenzymes called nonribosomal peptide synthetases (NRPSs). Each module is responsible for incorporation of a monomeric unit into the natural product peptide and is composed of individual domains that perform different catalytic reactions. Biochemical and bioinformatic investigations of these enzymes have uncovered the key principles of NRP synthesis, expanding the pharmaceutical potential of their enzymatic processes. Progress has been made in the manipulation of this biosynthetic machinery to develop new chemoenzymatic approaches for synthesizing novel pharmaceutical agents with increased potency. This review focuses on the recent discoveries and breakthroughs in the structural elucidation, molecular mechanism, and chemical biology underlying the discrete domains within NRPSs.     

Co-sheathed SiOx nanowires

We fabricated Co-coated SiO_x nanowires and investigated the effects of thermal annealing on their properties. The sputtering process resulted in the formation of a relatively smooth Co shell layer, whereas subsequent thermal annealing generated the Co₃O₄ phase. The photoluminescence (PL) spectrum was not changed by the Co-coating, whereas the thermal annealing induced new peaks in the yellow and ultraviolet regions. Possible emission mechanisms were discussed. Based on the magnetization measurements of the SiO_x-core/Co-shell nanowires, we obtained small and negligible hysteresis loops for the as-fabricated and thermal annealed samples, respectively.     

Charge fractionalization in nonchiral Luttinger systems

One-dimensional metals, such as quantum wires or carbon nanotubes, can carry charge in arbitrary units, smaller or larger than a single electron charge. However, according to Luttinger theory, which describes the low-energy excitations of such systems, when a single electron is injected by tunneling into the middle of such a wire, it will tend to break up into separate charge pulses, moving in opposite directions, which carry definite fractions f and (1-f) of the electron charge, determined by a parameter g that measures the strength of charge interactions in the wire. (The injected electron will also produce a spin excitation, which will travel at a different velocity than the charge excitations.) Observing charge fractionalization physics in an experiment is a challenge in those (nonchiral) low-dimensional systems which are adiabatically coupled to Fermi liquid leads. We theoretically discuss a first important step towards the observation of charge fractionalization in quantum wires based on momentum-resolved tunneling and multi-terminal geometries, and explain the recent experimental results of Steinberg et al. [H. Steinberg, G. Barak, A. Yacoby, L.N. Pfeiffer, K.W. West, B.I. Halperin, K. Le Hur, Nature Physics 4 (2008) 116].     

Effect of grain boundary on resistive magnetodielectric property of polycrystalline <Emphasis Type="Italic">γ</Emphasis>-Fe<Subscript>2</Subscript>O<Subscript>3</Subscript>

We have investigated the role of the grain boundary on the resistive magnetodielectric property of polycrystalline γ-Fe₂O₃ through impedance spectroscopy measurements. Depending on the sample preparation temperature, the dielectric constant of γ-Fe₂O₃ is significantly different especially at low frequencies (<10⁴ Hz) and high temperatures (>200 K). The value of the magnetodielectric effect at a specific frequency and the resonance frequency for the maximized magnetodielectric effect are different, although polycrystalline γ-Fe₂O₃ samples show a quite similar magnetoresistance. Through the experimentally obtained resistance ratio between the grain and the grain boundary, we can reproduce the magnetodielectric curves based on the Maxwell–Wagner model and the measured magnetoresistance.     

Large transverse motion and micro-bunching of trapped electrons in a wakefield accelerator driven by temporally-asymmetric laser pulses

The transverse oscillatory motion of trapped electrons under the influence of the laser fields trailing the temporally-asymmetric driving laser pulse was investigated with a theoretical model of the quasi-steady state solution of trapped electron dynamics in the cavity. Our studies show that the transverse oscillation of electrons accelerated in the ion cavity can increase drastically due to the resonance with the laser field of the tail of the temporally-asymmetric pulse. The motion of the accelerated electrons can be represented by a forced harmonic oscillation and it was confirmed by 2D particle-in-cell simulations. These transverse oscillations of beams lead to micro-bunching as well, which can be used for generation of femtosecond coherent radiations of keV range photon energies.     

Synthesis of new visible light active photocatalysts of Ba(In(1/3)Pb(1/3)M'(1/3))O3 (M' = Nb, Ta): a band gap engineering strategy based on electronegativity of a metal component

We have synthesized new, efficient, visible light active photocatalysts through the incorporation of highly electronegative non-transition metal Pb or Sn ions into the perovskite lattice of Ba(In(1/3)Pb(1/3)M'(1/3))O3 (M = Sn, Pb; M' = Nb, Ta). X-ray diffraction, X-ray absorption spectroscopic, and energy dispersive spectroscopic microprobe analyses reveal that tetravalent Pb or Sn ions exist in the B-site of the perovskite lattice, along with In and Nb/Ta ions. According to diffuse UV-vis spectroscopic analysis, the Pb-containing quaternary metal oxides Ba(In(1/3)Pb(1/3)M'(1/3))O3 possess a much narrower band gap (E(g) approximately 1.48-1.50 eV) when compared to the ternary oxides Ba(In(1/2)M'(1/2))O3 (E(g) approximately 2.97-3.30 eV) and the Sn-containing Ba(In(1/3)Sn(1/3)M'(1/3))O3 derivatives (E(g) approximately 2.85-3.00 eV). Such a variation of band gap energy upon the substitution is attributable to the broadening of the conduction band caused by the dissimilar electronegativities of the B-site cations. In contrast to the ternary or the Sn-substituted quaternary compounds showing photocatalytic activity under UV-vis irradiation, the Ba(In(1/3)Pb(1/3)M'(1/3))O3 compounds induce an efficient photodegradation of 4-chlorophenol under visible light irradiation (lambda > 420 nm). The present results highlight that the substitution of electronegative non-transition metal cations can provide a very powerful way of developing efficient visible light harvesting photocatalysts through tuning of the band structure of a semiconductive metal oxide.     

Evolution of the crystal and electronic structures of magnetic RuSr(2-x)La(x)GdCu2O8 superconductors upon La substitution

We have investigated systematically the effects of La substitution on the chemical bonding nature and physical properties of magnetic RuSr(2-x)La(x)GdCu2O8 superconductors. X-ray diffraction and energy dispersive spectroscopic microprobe analyses reveal that a fraction of Sr ions can be successfully replaced by La ions with the contraction of unit cell volume. According to electrical resistance and dc magnetization measurements, the La substitution gives rise to a significant reduction of superconducting transition temperature (T(c)) but to an increase of magnetic ordering temperature with depressed remanent magnetization. Ru K- and Cu K-edge X-ray absorption spectroscopic results clarify that average Ru and Cu oxidation states decrease upon the La substitution. On the basis of the spectroscopic evidences presented here, we are able to attribute the T(c) reduction upon the La substitution to the depletion of the hole density in CuO2 layers and the accompanying variation of magnetic coupling behavior to the change of Ru oxidation state.