Showing papers by "Xudong Xu published in 2023"
TL;DR: In this article , a septuple-deletion mutant of Synechococcus elongatus PCC 7942 was generated, and the effects of genome reduction on the growth and genome-wide transcription were investigated.
Abstract: Genome streamlining, as a natural process in the evolution of microbes, has become a common approach for generating ideal chassis cells for synthetic biology studies and industrial applications. However, systematic genome reduction remains a bottleneck in the generation of such chassis cells with cyanobacteria, due to very time-consuming genetic manipulations. Synechococcus elongatus PCC 7942, a unicellular cyanobacterium, is a candidate for systematic genome reduction, as its essential and nonessential genes have been experimentally identified. Here, we report that at least 20 of the 23 over 10 kb nonessential gene regions could be deleted and that stepwise deletions of these regions could be achieved. A septuple-deletion mutant (genome reduced by 3.8%) was generated, and the effects of genome reduction on the growth and genome-wide transcription were investigated. In the ancestral triple to sextuple mutants (b, c, d, e1), an increasingly large number of genes (up to 998) were upregulated relative to the wild type, while slightly fewer genes (831) were upregulated in the septuple mutant (f). In a different sextuple mutant (e2) derived from the quintuple mutant d, much fewer genes (232) were upregulated. Under the standard conditions in this study, the mutant e2 showed a higher growth rate than the wild type, e1 and f. Our results indicate that it is feasible to extensively reduce the genomes of cyanobacteria for generation of chassis cells and for experimental evolutionary studies.
TL;DR: In this article , a nonreversible heat-induced supramolecular gel based on natural products was reported for the first time, which showed a distinctive non-reversible phase transition from the liquid to gel state upon heating.
TL;DR: In this article , the authors investigated the whole plant of Actaea vaginata and found five cycloartane triterpene glycosides, including three new Actaeoside A−C (1−3) along with two known analogues, beesiosides E (4) and N (5).
TL;DR: In this paper , three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted to determine the binding modes of DSC, showing that DSC was differently bound to CA-SP1 with higher affinity than bevirimat.
Abstract: HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3′,3′-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat. To ascertain the binding modes of this derivative, further modification of compound 1 was conducted. Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted. Five new derivatives were synthesized, among which compound 3b showed significant activity against HIV-1NL4-3 with an EC50 value of 0.28 µM. The developed 3D-QSAR model resulted in great predictive ability with training set (r2 = 0.99, q2 = 0.55). Molecular docking studies were complementary to the 3D-QSAR analysis, showing that DSC was differently bound to CA-SP1 with higher affinity than that of bevirimat. MD studies revealed that the complex of the ligand and the protein was stable, with root mean square deviation (RMSD) values <2.5 Å. The above results provided valuable insights into the potential of DSC as a prototype to develop new antiviral agents.
TL;DR: In this paper , a diterpene supramolecular self-assembly system without additional chemicals, Nepebracteatalic acid nanoparticles (NA NPs), mediated through hydrogen bond, hydrophobic and electrostatic interaction, was proposed.
TL;DR: In this article , the role of low-index Pd(hkl) surfaces, including Pd (100), (111), and (110) planes, in ECSH of alkynes was investigated.
Abstract: Efficient electrochemical semi-hydrogenation (ECSH) of alkynes to alkenes is a promising alternative to traditional thermal semi-hydrogenation. Mechanistic understanding of crystal plane-dependent ECSH performance is extremely important for the subsequent catalyst design. Here, we investigate the role of low-index Pd(hkl) surfaces, including Pd (100), (111), and (110) planes, in ECSH of alkynes. As a result, alkyne conversion rate and alkene selectivity of Pd(hkl) surfaces follow the order of Pd (100) > Pd (111) > Pd (110). In situ Raman spectroscopic evidence indicates that the Pd (100) plane effectively enhances the formation of K+ ion hydrated water and two-coordinated hydrogen-bonded water to accelerate semi-hydrogenation rate and improve alkene selectivity, respectively. The order of the ability to regulate the interfacial water structure is ideally consistent with that of ECSH performance on Pd(hkl) surfaces. Pd nanocubes enclosed by the (100) surface exhibit excellent ECSH activity, alkene selectivity, and cycling stability. These findings demonstrate that the interfacial water structure is crystal plane-dependent, which is the determining factor for ECSH.
TL;DR: In this paper , a gram-scale synthesis method of Tournefolic acid B (TAB) was established and the structure-activity relationship of its analogs was discussed, and the total synthesis of TAB was completed in 10 steps with an overall yield of 13%.
Abstract: Traditional Chinese medicine has been proven to be of great significance in cardioprotective effects. Clinopodium chinense (Lamiaceae) has unique advantages in the treatment and prevention of cardiovascular diseases. Tournefolic acid B (TAB) was proven to be a potent component against myocardial ischemia reperfusion injury (MIRI) from Clinopodium chinense (Lamiaceae). This article will attempt to establish a gram-scale synthesis method of TAB and discuss the structure-activity relationship of its analogs. The total synthesis of TAB was completed in 10 steps with an overall yield of 13%. In addition, analogs were synthesized, and their cardioprotective activity was evaluated on the hypoxia/reoxygenation of H9c2 cells. Amidation of the acid position is helpful to the activity, while methylation of phenolic hydroxyl groups greatly decreased the cardioprotective activity. The easily prepared azxepin analogs also showed cardioprotective activity. Most of the clogP values calculated by Molinspiration ranged from 2.5 to 5, which is in accordance with Lipinski’s rule of 5. These findings represent a novel kind of cardioprotective agent that is worthy of further study.