Teleocidins are natural products belonging to the indole alkaloid family and show potent protein kinase C activation activity. The structural feature of teleocidins is an indole-fused nine-membered ...lactam ring structure. Due to their unique structures and strong biological activities, many total synthesis and biosynthetic studies of teleocidins have been performed. Teleocidin biosynthesis involves interesting enzymatic reactions that are challenging in organic synthesis, including oxidative intramolecular C–N bond-forming reactions, regio- and stereo-selective reverse prenylation reactions, and methylation-triggered terpene cyclization. This review summarizes the recent research on functional and structural analyses, as well as enzyme engineering, of teleocidin biosynthetic enzymes.
Aromatic prenyltransferases (PTases), including ABBA-type and dimethylallyl tryptophan synthase (DMATS)-type enzymes from bacteria and fungi, play important role for diversification of the natural ...products and improvement of the biological activities. For a decade, the characterization of enzymes and enzymatic synthesis of prenylated compounds by using ABBA-type and DMATS-type PTases have been demonstrated. Here, I introduce several examples of the studies on chemoenzymatic synthesis of unnatural prenylated compounds and the enzyme engineering of ABBA-type and DMATS-type PTases.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Consider an intersection measure ℓtIS of p independent (possibly different) m‐symmetric Hunt processes up to time t in a metric measure space E with a Radon measure m. We derive a Donsker–Varadhan ...type large deviation principle for the normalized intersection measure t−pℓtIS on the set of finite measures on E as t→∞, under the condition that t is smaller than life times of all processes. This extends earlier work by W. König and C. Mukherjee 16, in which the large deviation principle was established for the intersection measure of p independent N‐dimensional Brownian motions before exiting some bounded open set D⊂RN. We also obtain the asymptotic behavior of logarithmic moment generating function, which is related to the results of X. Chen and J. Rosen 7 on the intersection measure of independent Brownian motions or stable processes.
Our results rely on assumptions about the heat kernels and the 1‐order resolvents of the processes, hence include rich examples. For example, the assumptions hold for p∈Z with 2≤p<p∗ when the processes enjoy (sub‐)Gaussian type or jump type heat kernel estimates, where p∗ is determined by the Hausdorff dimension of E and the so‐called walk dimensions of the processes.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This study alleviates the low operating temperature constraint of Si qubits. A qubit is a key element for quantum sensors, memories, and computers. Electron spin in Si is a promising qubit, as it ...allows both long coherence times and potential compatibility with current silicon technology. Si qubits have been implemented using gate-defined quantum dots or shallow impurities. However, operation of Si qubits has been restricted to milli-Kelvin temperatures, thus limiting the application of the quantum technology. In this study, we addressed a single deep impurity, having strong electron confinement of up to 0.3 eV, using single-electron tunnelling transport. We also achieved qubit operation at 5-10 K through a spin-blockade effect based on the tunnelling transport via two impurities. The deep impurity was implemented by tunnel field-effect transistors (TFETs) instead of conventional FETs. With further improvement in fabrication and controllability, this work presents the possibility of operating silicon spin qubits at elevated temperatures.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Endoperoxide-containing natural products are a group of compounds with structurally unique cyclized peroxide moieties. Although numerous endoperoxide-containing compounds have been isolated, the ...biosynthesis of the endoperoxides remains unclear. NvfI from Aspergillus novofumigatus IBT 16806 is an endoperoxidase that catalyzes the formation of fumigatonoid A in the biosynthesis of novofumigatonin. Here, we describe our structural and functional analyses of NvfI. The structural elucidation and mutagenesis studies indicate that NvfI does not utilize a tyrosyl radical in the reaction, in contrast to other characterized endoperoxidases. Further, the crystallographic analysis reveals significant conformational changes of two loops upon substrate binding, which suggests a dynamic movement of active site during the catalytic cycle. As a result, NvfI installs three oxygen atoms onto a substrate in a single enzyme turnover. Based on these results, we propose a mechanism for the NvfI-catalyzed, unique endoperoxide formation reaction to produce fumigatonoid A.
Anditomin and its precursors, andilesins, are fungal meroterpenoids isolated from Aspergillus variecolor and have unique, highly oxygenated chemical structures with a complex bridged-ring system. ...Previous isotope-feeding studies revealed their origins as 3,5-dimethylorsellinic acid and farnesyl pyrophosphate and suggested the possible involvement of a Diels–Alder reaction to afford the congested bicyclo2.2.2octane core structure of andilesins. Here we report the first identification of the biosynthetic gene cluster of anditomin and the determination of the complete biosynthetic pathway by characterizing the functions of 12 dedicated enzymes. The anditomin pathway actually does not employ a Diels–Alder reaction, but involves the nonheme iron-dependent dioxygenase AndA to synthesize the bridged-ring by an unprecedented skeletal reconstruction. Another dioxygenase, AndF, is also responsible for the structural complexification, generating the end product anditomin by an oxidative rearrangement.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Teleocidins are potent protein kinase C activators, and possess a unique indole‐fused nine‐membered lactam structure. Teleocidin biosynthesis starts from the formation of a dipeptide by non‐ribosomal ...peptide synthetase (NRPS), followed by oxidative C−N bond formation by a cytochrome P450 oxidase, reverse‐prenylation by a prenyltransferase, and methylation‐initiated terpene cyclization by a C‐methyltransferase. This minireview focuses on recent research progress toward the elucidation of the molecular basis for the remarkable P450‐catalyzed intramolecular C−N bond‐forming reaction, which is challenging in synthetic chemistry, to generate the indolactam scaffold. In addition, precursor‐directed biosynthesis with the promiscuous P450 enzymes led to the formation of a series of unnatural and novel molecular scaffolds, including a sulfur‐substituted indolactam with a different conformation from that of indolactam V.
Enzymatic formation of indolactam: This minireview focuses on recent research progress on the elucidation of the molecular basis for the P450‐catalyzed remarkable intramolecular C−N bond‐forming reaction to generate the indolactam scaffold. In addition, precursor‐directed biosynthesis led to formation of a series of unnatural novel molecular scaffolds including a sulfur‐substituted indolactam, conformation of which is significantly different from that of indolactam V.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This study investigates the influence of heat treatment on the anisotropic plastic deformation behaviors of 6016-O and 6016-T4 aluminum alloy sheets. The two material samples were fabricated from the ...same lot and, therefore, have the same grain size and crystallographic texture. Biaxial tensile tests using both cruciform and tubular specimens are performed for many proportional stress paths in the first quadrant of stress space. The test results reveal that the degree of differential hardening (DH) is much larger in 6016-T4 than in 6016-O. It is shown that the work contour shape of 6016-O is controlled by crystallographic texture, whereas that of 6016-T4 presumably depends on GP-zones as well. From the biaxial stress test data, an appropriate yield function for each material is determined and employed in the finite element analysis of the hole expansion forming process. It was found that the Yld2000-2d yield function provides proper material representations of the plastic behavior of both material samples in the sense that it correctly predicts the fracture or localized neck locations, which occurs in the hole edge vicinity. For 6016-O, the thickness strain profile predicted with the Yld2000-2d yield function, which accounts for the DH of the material, is in better agreement with the experimental results than that obtained with the isotropic hardening model. For 6016-T4, the Yld2000-2d yield function with an exponent of 8 with the isotropic hardening assumption leads to a fair prediction of the experimental data. In order to enhance the accuracy of forming simulations for 6016-T4, it is necessary to develop a material model that is capable of reproducing the significant DH resulting from the GP-zones.
•Biaxial tensile tests of AA6016-O and -T4 with same texture are performed.•The degree of differential hardening is much larger for AA6016-T4 than for -O.•The Yld2000-2d yield function gives proper material for both test materials.•Positions of localized necking in hole expansion forming are correctly predicted.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Expanding the range of genetically encoded metal coordination environments accessible within tunable protein scaffolds presents excellent opportunities for the creation of metalloenzymes with ...augmented properties and novel activities. Here, we demonstrate that installation of a noncanonical N δ-methyl histidine (NMH) as the proximal heme ligand in the oxygen binding protein myoglobin (Mb) leads to substantial increases in heme redox potential and promiscuous peroxidase activity. Structural characterization of this catalytically modified myoglobin variant (Mb NMH) revealed significant changes in the proximal pocket, including alterations to hydrogen-bonding interactions involving the prosthetic porphyrin cofactor. Further optimization of Mb NMH via a combination of rational modification and several rounds of laboratory evolution afforded efficient peroxidase biocatalysts within a globin fold, with activities comparable to those displayed by nature’s peroxidases.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
PDF
