Creation of cytochrome P450 catalysis depending on a non-natural cofactor for fatty acid hydroxylation

Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.

Investigation on the electrode surface roughness effects on a repetitive self-breakdown gas switch

In this work,the influence of the electrode surface roughness on the self-breakdown gas switch is investigated by physical analysis,computer simulation and experiment.Cu-W electrodes of different surface roughness were tested under the conditions of a pulse repetitive frequency of50 Hz,self-breakdown voltage of~30 kV,and peak current of~2 k A for~93000 shots(the total charge transferred was~15 C).The coefficients of variation of the self-breakdown voltage of Cu-W 0.8,Cu-W 3.2 and Cu-W 12.5 electrodes were~2.95%,~1.62%and~1.16%,respectively.With the increase of electrode roughness,the erosion area decreased continuously,indicating that the breakdown positions were more stable and the coefficient of variation of breakdown voltage decreased.The method showed that decreasing the coefficient of variation of the self-breakdown voltage by increasing the surface roughness of electrode greatly improves the stability of the self-breakdown switch,which is significant for their application in compact highpower pulse power devices over a long time with stable operation.

3D genomic organization in cancers

Background:The hierarchical three-dimensional(3D)architectures of chromatin play an important role in fundamental biological processes,such as cell differentiation,cellular senescence,and transcriptional regulation.Aberrant chromatin 3D structural alterations often present in human diseases and even cancers,but their underlying mechanisms remain unclear.Results:3D chromatin structures(chromatin compartment A/B,topologically associated domains,and enhancerpromoter interactions)play key roles in cancer development,metastasis,and drug resistance.Bioinformatics techniques based on machine learning and deep learning have shown great potential in the study of 3D cancer genome.Conclusion:Current advances in the study of the 3D cancer genome have expanded our understanding of the mechanisms underlying tumorigenesis and development.It will provide new insights into precise diagnosis and personalized treatment for cancers.

ECharts: A declarative framework for rapid construction of web-based visualization

While there have been a dozen of authoring systems and programming toolkits for visual design and development,users who do not have programming skills,such as data analysts or interface designers,still may feel cumbersome to efficiently implement a web-based visualization.In this paper,we present ECharts,an open-sourced,web-based,cross-platform framework that supports the rapid construction of interactive visualization.The motivation is driven by three goals:easy-touse,rich built-in interactions,and high performance.The kernel of ECharts is a suite of declarative visual design language that customizes built-in chart types.The underlying streaming architecture,together with a high-performance graphics renderer based on HTML5 canvas,enables the high expandability and performance of ECharts.We report the design,implementation,and applications of ECharts with a diverse variety of examples.We compare the utility and performance of ECharts with C3.js,HighCharts,and Chart.js.Results of the experiments demonstrate the efficiency and scalability of our framework.Since the first release in June 2013,ECharts has iterated 63 versions,and attracted over 22,000 star counts and over 1700 related projects in the GitHub.ECharts is regarded as a leading visualization development tool in the world,and ranks the third in the GitHub visualization tab.

Potassium Tantalate K6Ta10.8O30 with Tungsten Bronze Structure and Its Photocatalytic Property

With the tunable and flexible physicochemical properties, tantalate photocatalysts with tungsten bronze struc- ture are worth being studied. In this work, we successfully synthesized a novel potassium tantalate K6Talo.8030 with tungsten bronze structure using a facile solid-state reaction route. The effects of calcination time on the phase com- position, morphology and crystallinity of the obtained samples were studied by XRD and SEM analyses. In addition, the photocatalytic activity of the samples was evaluated by the degradation of ARG dye under UV light irradiation. The results indicated that the K6Talo.8030 showed high photocatalytic activity for degradation of ARG and the pho- tocatalytic degradation of ARG followed the first order kinetics. Furthermore, the possible photocatalytic mecha- nism of the K6TamsO30 photocatalyst was proposed based on tungsten bronze structure feature and the scavengers experimental results. This study would give a new insight into tantalate photocatalysts.

Synthesis of Donor-Acceptorπ-Conjugated Macrocycles by Post-Functionalization

Main observation and conclusion In this paper,two novel donor-acceptor(D-A)macrocyclic compounds 5 and 7 were successfully synthesized by post-functionalization of a planar dimer macrocycle(1)and a highly twisted trimer macrocycle(2),respectively,via controllable oxidation of methoxy groups and condensation between diketones and phenylenediamine in succession.Compared with unembellished 9,10-dimethoxyphenanthrene,the resultant dibenzo[a,c]phenazine motif is electron-deficient rather than electron-rich,yielding two D-Aπ-conjugated macrocycles with more contractive energy gaps.Density functional theory(DFT)calculations further support the unequivocal evidence of the D-A properties of macrocycles 5 and 7.The difference of their photophysical properties was investigated by the aid of ultraviolet-visible absorption and fluorescence spectrophotometers.Furthermore,the stacking patterns of 7 and its contrastπ-conjugated macrocycle trimer(2)were compared via the analysis of X-ray single crystal,in which the electron-deficient dibenzo[a,c]phenazine unit provides extra interaction sites,resulting in orderly arrangement of 7 in the solid state.