Simulations of the Characteristics of the Entropy Mode in Dipole-Magnetic-Confined Plasmas.

Plasmas confined in a dipole magnetic field widely exist in both space and laboratories, and this kind of plasma draws much attention from researchers both in plasma physics and in space science. In this paper, the characteristics of the collisionless electrostatic instability of the entropy mode in a dipole-magnetic-confined plasma are simulated with the linear gyrokinetic model. It is found that the entropy mode can be generated in dipole-magnetic-confined plasmas, and there are two typical stages of the entropy mode, with another transitional stage at different values of η. The main instability changes from the ion diamagnetic drift to the electronic diamagnetic drift as η becomes larger. In addition, the MHD mode predicts that the most stable point is at η~2/3 when k⟂ρi << 1. However, we find that η and k⟂ρi are coupled with each other, and the most stable point of the mode moves gradually to η~1 as k⟂ρi increases. There is a peak value for the entropy mode growth rate around k⟂ρi~1.0, and more complicated modes are induced so that the dispersion relation has been changed when the driving force of the plasma pressure gradient effect is obvious. For example, the characteristics of the interchange-like modes gradually emerge when the driving effect of the plasma pressure becomes stronger. Further investigations should be taken to reveal the characteristics of the entropy mode in magnetospheric plasmas.

Investigation on the near-field cutoff effect in a subwavelength plasma shell with near-zero permittivity.

Although the plasma-induced receiving and radiating near-field cutoff phenomena in the subwavelength regime are found of crucial importance in electromagnetic (EM) signal transmissions and plasma property studies, their mechanisms to a large extent remain unclear and undistinguished. In this paper, in the perspective of field and energy transfer, it is demonstrated that the cutoff in the near-field regime is completely different from that in the geometric optical regime. Results show that, for the receiving mode, epsilon-near-zero (ENZ) plasmas can be treated as a nearly ideal EM fluid, and thus, EM waves are restricted into the plasma channel. For the radiating mode, on the other hand, it is the destructive interference between the electric dipole fields of the antenna and the ENZ plasma that results in vanishing far-field radiation. As an important supplement to the existing cutoff theories, our results not only offer clearer physical insights into the near-field cutoff effect but also provide a helpful reference for cutoff-related practical applications in various frequency bands.

Fungal P450 Deconstructs the 2,5-Diazabicyclo[2.2.2]octane Ring En Route to the Complete Biosynthesis of 21R-Citrinadin A.

Prenylated indole alkaloids (PIAs) possess great structural diversity and show biological activities. Despite significant efforts in investigating the biosynthetic mechanism, the key step in the transformation of 2,5-diazabicyclo[2.2.2]octane-containing PIAs into a distinct class of pentacyclic compounds remains unknown. Here, using a combination of gene deletion, heterologous expression, and biochemical characterization, we show that a unique fungal P450 enzyme CtdY catalyzes the cleavage of the amide bond in the 2,5-diazabicyclo[2.2.2]octane system, followed by a decarboxylation step to form the 6/5/5/6/6 pentacyclic ring in 21R-citrinadin A. We also demonstrate the function of a subsequent cascade of stereospecific oxygenases to further modify the 6/5/5/6/6 pentacyclic intermediate en route to the complete 21R-citrinadin A biosynthesis. Our findings reveal a key enzyme CtdY for the pathway divergence in the biosynthesis of PIAs and uncover the complex late-stage post-translational modifications in 21R-citrinadin A biosynthesis.

An NmrA-like enzyme-catalysed redox-mediated Diels-Alder cycloaddition with anti-selectivity.

The Diels-Alder cycloaddition is one of the most powerful approaches in organic synthesis and is often used in the synthesis of important pharmaceuticals. Yet, strictly controlling the stereoselectivity of the Diels-Alder reactions is challenging, and great efforts are needed to construct complex molecules with desired chirality via organocatalysis or transition-metal strategies. Nature has evolved different types of enzymes to exquisitely control cyclization stereochemistry; however, most of the reported Diels-Alderases have been shown to only facilitate the energetically favourable diastereoselective cycloadditions. Here we report the discovery and characterization of CtdP, a member of a new class of bifunctional oxidoreductase/Diels-Alderase, which was previously annotated as an NmrA-like transcriptional regulator. We demonstrate that CtdP catalyses the inherently disfavoured cycloaddition to form the bicyclo[2.2.2]diazaoctane scaffold with a strict α-anti-selectivity. Guided by computational studies, we reveal a NADP+/NADPH-dependent redox mechanism for the CtdP-catalysed inverse electron demand Diels-Alder cycloaddition, which serves as the first example of a bifunctional Diels-Alderase that utilizes this mechanism.

Multiplex Base-Editing Enables Combinatorial Epigenetic Regulation for Genome Mining of Fungal Natural Products.

Genome mining of cryptic natural products (NPs) remains challenging, especially in filamentous fungi, owing to their complex genetic regulation. Increasing evidence indicates that several epigenetic modifications often act cooperatively to control fungal gene transcription, yet the ability to predictably manipulate multiple genes simultaneously is still largely limited. Here, we developed a multiplex base-editing (MBE) platform that significantly improves the capability and throughput of fungal genome manipulation, leading to the simultaneous inactivation of up to eight genes using a single transformation. We then employed MBE to inactivate three negative epigenetic regulators combinatorially in Aspergillus nidulans, enabling the activation of eight cryptic gene clusters compared to the wild-type strains. A group of novel NPs harboring unique cichorine and polyamine hybrid chemical scaffolds were identified, which were not reported previously. We envision that our scalable and efficient MBE platform can be readily applied in other filamentous fungi for the genome mining of novel NPs, providing a powerful approach for the exploitation of fungal chemical diversity.

Achieving tunable Kerker-type invisibility for a radiation-enhanced electrically small antenna.

Low-temperature gaseous plasmas exhibit great potential in designing tunable and reconfigurable electromagnetic devices. In this paper, based on an overdense-underdense core-shell plasma structure, tunable Kerker-type invisibility for a radiation-enhanced electrically small antenna is achieved, where dominant scattering direction can be mutated between backward and forward while omnidirectional invisibility and signal enhancement are maintained. Moreover, by electromagnetic multipole decompositions, it is shown that the underdense outer plasma with a negative polarizability is able to weaken the strength and modulate the phase of the electric dipolar scattering component (a_{1}), while the magnetic dipolar term (b_{1}) nearly remains unchanged. Consequently, quasi-first and -second Kerker conditions are fulfilled near the cutoff band of a_{1}.

Biosynthesis of DNA-Alkylating Antitumor Natural Products.

DNA-alkylating natural products play an important role in drug development due to their significant antitumor activities. They usually show high affinity with DNA through different mechanisms with the aid of their unique scaffold and highly active functional groups. Therefore, the biosynthesis of these natural products has been extensively studied, especially the construction of their pharmacophores. Meanwhile, their producing strains have evolved corresponding self-resistance strategies to protect themselves. To further promote the functional characterization of their biosynthetic pathways and lay the foundation for the discovery and rational design of DNA alkylating agents, we summarize herein the progress of research into DNA-alkylating antitumor natural products, including their biosynthesis, modes of action, and auto-resistance mechanisms.

Discovery of glycosylated naphthacemycins and elucidation of the glycosylation.

Two glycosylated naphthacemycins (naphthacemycins D1 and D2) were identified in Streptomyces sp. N12W1565. These two compounds not only showed antimicrobial potential against bacteria but also exhibited more aqueous solubility than naphthacemycins. Furthermore, the whole genome of Streptomyces sp. N12W1565 has been sequenced, the natY gene, located outside the biosynthetic gene cluster encoding a D-glucose glycosyltransferase, was identified to mediate glycosylation in the phenolic hydroxyl of the naphthacemycin core scaffold. Glycosyltransferase was elucidated in vitro by using a homologous enzyme, which showed potential as a biocatalyst.

Unraveling the biosynthesis of penicillenols by genome mining PKS-NRPS gene clusters in Penicillium citrinum.

Penicillenols belong to the family of tetramic acids with anticancer and antibacterial activities. Here, we report the discovery of the biosynthetic gene cluster (pnc) for penicillenol A1 and E in Penicillium citrinum ATCC9849 by genome mining. We discover the pnc cluster based on the results of gene deletions in P. citrinum and gene cluster heterologous expression in Aspergillus nidulans. We also propose the assembly line of the PKS module in PncA with the reduction by PncB provides a highly reduce polyketide chain to be further linked with an L-threonine molecule and released from PncA to produce penicillenol E. Further formation of penicillenol A1 requires the N-methylation of tetramic acid group by PncC. Our work deepens the understanding of the biosynthetic logic for N-methylated tetramic acids and contributes to the discovery of new penicillenols by genome mining.

Activation and Characterization of Cryptic Gene Cluster: Two Series of Aromatic Polyketides Biosynthesized by Divergent Pathways.

One biosynthetic gene cluster (BGC) usually governs the biosynthesis of a series of compounds exhibiting either the same or similar molecular scaffolds. Reported here is a multiplex activation strategy to awaken a cryptic BGC associated with tetracycline polyketides, resulting in the discovery of compounds having different core structures. By constitutively expressing a positive regulator gene in tandem mode, a single BGC directed the biosynthesis of eight aromatic polyketides with two types of frameworks, two pentacyclic isomers and six glycosylated tetracyclines. The proposed biosynthetic pathway, based on systematic gene inactivation and identification of intermediates, employs two sets of tailoring enzymes with a branching point from the same intermediate. These findings not only provide new insights into the role of tailoring enzymes in the diversification of polyketides, but also highlight a reliable strategy for genome mining of natural products.

Note: Stability control of intermediate frequencies of a three laser far-infrared polarimeter-interferometer system.

Stability of the intermediate frequency (IF) in the far-infrared polarimeter-interferometer diagnostic system is critically important for the long pulse discharge experiments on the EAST tokamak. In this note, a real-time remote/local IF stability control system is described. The measured plasma parameters, including the Faraday rotation angle, electron density, lower hybrid wave, and plasma current, are obtained with the aid of this newly developed IF stability control system.