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Synthetic and Systems Biotechnology 2024年第2期9卷 187-195页

作者： Zetian Qiu Xiaohui liu Jie Yu Yushuo Zhao Guang-Rong Zhao shengying li Kun liu Lei Du li Ma State Key Laboratory of Microbial Technology Shandong UniversityQingdaoShandong266237China Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityYaguan Road 135Jinnan DistrictTianjin300350China School of Health Management Hengxing UniversityQingdaoShandong266100China

Benzyl and phenylpropanoid acids are widely used in organic synthesis of fine chemicals,such as pharmaceuticals and ***,biocatalysis of these acids has received less attention than chemical *** of the main challenges for biological production is the limited availability of alcohol dehydrogenases and aldehyde *** microorganisms are potential sources of these *** this study,129 alcohol dehydrogenases and 42 aldehyde dehydrogenases from Corynebacterium glutamicum,Pseudomonas aeruginosa,and Bacillus subtilis were identified and explored with various benzyl and phenylpropanoid alcohol and aldehyde substrates,among which four alcohol dehydrogenases and four aldehyde dehydrogenases with broad substrate specificity and high catalytic activity were ***,a cascade whole-cell catalytic system including ADH-90,ALDH-40,and the NAD(P)H oxidase LreNox was established,which showed high efficiency in converting cinnamyl alcohol and p-methylbenzyl alcohol into the respective carboxylic ***,this biocatalytic system can be easily scaled up to gram-level production,facilitating preparation purposes.

关键词： Benzyl acids Phenylpropanoid acids Alcohol dehydrogenases Aldehyde dehydrogenases Whole-cell catalysis

故障修复增强的抗差滤波PDR/GNSS行人导航方法

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仪器仪表学报 2024年第2期45卷 233-242页

作者：李圣英孟骞姜颖颖王立辉东南大学仪器科学与工程学院南京210096 微惯性仪表与先进导航技术教育部重点实验室南京210096

针对复杂环境下智能手机卫星信号容易受到干扰而引起组合导航精度降低的问题,提出一种基于故障修复的抗差滤波行人导航方法。该法首先利用等价权因子实时调整观测权值,以有效地减少观测粗差对组合导航精度的影响。其次,针对松组合系统... 详细信息

针对复杂环境下智能手机卫星信号容易受到干扰而引起组合导航精度降低的问题,提出一种基于故障修复的抗差滤波行人导航方法。该法首先利用等价权因子实时调整观测权值,以有效地减少观测粗差对组合导航精度的影响。其次,针对松组合系统没有观测冗余的模型局限性,将抗差扩展卡尔曼滤波检测区间分为无故障、偏离和异常3段。无故障时,不做处理;出现偏离时,对观测值进行降权处理;异常情况下,利用预测新息对故障进行幅值修复,进而修正观测值。实际实验结果表明,当GNSS出现单历元故障时,经典的抗差滤波方法能够有效提高智能手机PDR/GNSS组合导航定位精度,其北向最大误差由7.27 m减小为3.20 m,东向最大位置误差由24.01 m减小为6.60 m;在GNSS出现多历元连续故障时,所提出的故障修复增强的抗差滤波方法相比经典的抗差滤波方法的平均定位误差下降了50%以上。

关键词：行人导航 PDR/GNSS松组合抗差滤波故障修复智能手机

Effects of timber infill walls on the seismic behavior of traditional Chinese timber frames

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Earthquake Engineering and Engineering Vibration 2022年第4期21卷 999-1018页

作者： Xie Qifang Zhang Baozhuang li shengying Wu Fanfan Yang Huifeng Key Laboratory of Earthquake Engineering and Engineering Vibration Institute of Engineering MechanicsChina Earthquake AdministrationHarbin 150080China School of Civil Engineering Xi’an University of Architecture and TechnologyXi′an 710055China China Coal Xi′an Design Engineering Co. Ltd.Xi′an 710055China College of Civil Engineering Nanjing Tech UniversityNanjing 211816China

This study investigates the enhanced effect of timber infill walls on the seismic behavior of traditional Chinese timber *** 1/2 scaled traditional Chinese timber infill walls(TIWs),two 1/2 scaled timber frames with timber infill walls(TFTIWs)and one 1/2 scaled timber frame(TF)were fabricated and tested under low-cyclic reversed *** failure modes,strength,stiffness,and energy consumption capacity of the TIWs and the TFTIWs were obtained,and the effects of the TIWs on the seismic performance of the TFTIWs were *** results showed that the TIWs can increase the stiffness and ultimate bearing capacity of the TF,up to 60%and 80%,*** strength degradation coefficient of the TFTIWs was slightly higher than that of the TF when the inter-story drift ratio exceeded 0.02 rad,and the TIWs helped to mitigate the strength degradation of the *** was also found that the TFTIWs had a higher cumulative energy dissipation when compared with the TF(up to a 60%increase),indicating the TIWs had reasonably good energy dissipation *** the TIWs generated a solid contribution to the carrying capacity and energy dissipation of the TF,the lateral drift thresholds were 1/100 and 1/43 of the column height,***,the TIWs and TFTIWs presented a good ductility,and the TIW could effectively reduce the pull-out amount of the tenon from the mortise of the TF;however,the TIWs had little influence on the stiffness degradation level or improvement of the ductility of the TF.

关键词： traditional Chinese timber frame timber infill wall mortise-tenon joint cyclic loading test seismic behavior

Preparation and photocatalytic activity of PANI/TiO_2 composite film

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Rare Metals 2007年第1期26卷 1-7页

作者： GAO Jinzhang li shengying YANG Wu ZHAO Guohu BO lili SONG li College of Chemistry and Chemical Engineering Northwest Normal University Gansu Key Lab of Polymer Materials Lanzhou 730070 China

A PANI/TiO2 composite film deposited on the glass surface was successfully prepared using sol-gel dip-coating technique and chemical oxidation method. The film was characterized using XRD, AFM, and UV. The result showed that the TiO2 film consists of both cuboid-shaped and anatase-phased TiO2 nanoparticles. The average grain size of TiO2 in the film was approximately 20 nm. After coating with PANI, the particle was changed into irregular spherical-shaped and the size was increased up to approximately 35 nm in diameter. UV-Vis spectroscopy analysis indicated that the coating of TiO2 with PANI would result in an enhancement of photocatalytic efficiency and an extension of the photoresponse of TiO2. The band gap of the PANI/TiO2 film was 3.18 eV. The photocatalytic property of the film was evaluated by the degradation of rhodamine-B. It was found that 67.1% and 83.2% of rhodamine-B could be degraded under sunlight and UV irradiation within 120 min using the PANI/TiO2 composite t-tim as photocatalyst.

关键词： PANI/TiO2 film sol-gel method chemical oxidation method photocatalysis rhodamine-B

Cytochrome P450s in algae:Bioactive natural product biosynthesis and light-driven bioproduction

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2832-2844页

作者： Shanmin Zheng Jiawei Guo Fangyuan Cheng Zhengquan Gao Lei Du Chunxiao Meng shengying li Xingwang Zhang School of life Sciences Shandong University of TechnologyZibo 255000China State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266237China School of Pharmacy Binzhou Medical UniversityYantai 264003China Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China

Algae are a large group of photo synthetic organisms responsible for approximately half of the earth’s total *** addition to their fundamental ecological roles as oxygen producers and as the food base for almost all aquatic life,algae are also a rich source of bioactive natural products,including several clinical *** P450 enzymes(P450s) are a superfamily of biocatalysts that are extensively involved in natural product biosynthesis by mediating various types of *** the post-genome era,a growing number of P450 genes have been discovered from algae,indicating their important roles in algal ***,the functional studies of algal P450s remain *** from the recent technical advances in algae cultivation and genetic manipulation,the researches on P450s in algal natural product biosynthesis have been approaching to a new ***,some photoauto trophic algae have been developed into "photo-bioreactors" for heterologous P450s to produce high-value added pharmaceuticals and chemicals in a carbon-neutral or carbon-negative ***,we comprehensively review these advances of P450 studies in algae from 2000 to 2021.

关键词： Natural product biosynthesis Algal pharmaceuticals Cytochrome P450 enzymes Algae light-driven bioproduction

Enzymatic synthesis of indigo derivatives by tuning P450 BM3 peroxygenases

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Synthetic and Systems Biotechnology 2023年第3期8卷 452-461页

作者： li Ma Tianjian Sun Yunjie liu Yue Zhao Xiaohui liu Yuxuan li Xinwei Chen lin Cao Qianqian Kang Jiawei Guo Lei Du Wei Wang shengying li State Key Laboratory of Microbial Technology Shandong UniversityQingdao266237China School of Materials Science and Engineering Ocean University of ChinQingdao266100China Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao266237China

Indigoids,a class of bis-indoles,have long been applied in dyeing,food,and pharmaceutical ***,interest in these‘old’molecules has been renewed in the field of organic semiconductors as functional building blocks for organic electronics due to their excellent chemical and physical ***,these indigo derivatives are difficult to access through chemical *** this study,we engineer cytochrome P450 BM3 from an NADPH-dependent monooxygenase to peroxygenases through directed evolution.A select number of P450 BM3 variants are used for the selective oxidation of indole derivatives to form different indigoid pigments with a spectrum of *** the prepared indigoid organic photocatalysts,a majority of indigoids demonstrate a reduced band gap than indigo due to the increased light capture and improved charge separation,making them promising candidates for the development of new organic electronic ***,we present a useful enzymatic approach with broad substrate scope and cost-effectiveness by using low-cost H2O2 as a cofactor for the preparation of diversified indigoids,offering versatility in designing and manufacturing new dyestuff and electronic/sensor components.

关键词： Cytochrome P450 enzymes P450 BM3 peroxygenase Indigoids Dyestuff Organic electronics

Structure-guided manipulation of the regioselectivity of the cyclosporine A hydroxylase CYP-sb21 from Sebekia benihana

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Synthetic and Systems Biotechnology 2020年第3期5卷 236-243页

作者： Fengwei li li Ma Xingwang Zhang Jingfei Chen Feifei Qi Yinyue Huang Zepeng Qu lishan Yao Wei Zhang Eung-Soo Kim shengying li State Key Laboratory of Microbial Technology Shandong UniversityQingdaoShandong266237China Shandong Provincial Key Laboratory of Synthetic Biology CAS Key Laboratory of BiofuelsQingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdaoShandong266101China Department of Biological Engineering Inha UniversityIncheon22212South Korea Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdaoShandong266237China

The cytochrome P450 enzyme CYP-sb21 from the rare actinomycete Sebekia benihana is capable of hydroxylating the immunosuppressive drug molecule cyclosporine A(CsA)primarily at the 4th N-methyl leucine(MeLeu4),giving rise toγ-hydroxy-N-methyl-L-Leu4-CsA(CsA-4-OH).This oxidative modification of CsA leads to dramatically reduced immunosuppressive activity while retaining the hair growth-promoting side-effect,thus demonstrating great application potential in both pharmaceutical and cosmetic ***,this P450 enzyme also hydroxylates CsA at the unwanted position of the 9th N-methyl leucine(MeLeu9),indicating that the regioselectivity needs to be improved for the development of CsA-4-OH into a commercial hair growth ***,we report the crystal structure of CYP-sb21 in its substrate-free form at 1.85Å.Together with sequence and 3D structure comparisons,Autodock-based substrate docking,molecular dynamics(MD)simulation,and site-directed mutagenesis,we identified a number of key residues including R294,E264,and M179 that can improve catalytic efficiency or change the regioselectivity of CYP-sb21 towards CsA,setting the stage for better enzymatic preparation of *** study also provides new insights into the substrate recognition and binding mechanism of P450 enzymes that accommodate bulky substrates.

关键词： Cytochrome P450 monooxygenase Crystal structure Cyclosporine A Regioselectivity Hair growth stimulator

Development of MEMS directed evolution strategy for multiplied throughput and convergent evolution of cytochrome P450 enzymes

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Science China(life Sciences) 2022年第3期65卷 550-560页

作者： li Ma Fengwei li Xingwang Zhang Hui Chen Qian Huang Jing Su Xiaohui liu Tianjian Sun Bo Fang Kun liu Dandan Tang Dalei Wu Wei Zhang Lei Du shengying li State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266237China Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China Shandong Provincial Key Laboratory of Synthetic Biology Qingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdao 266101China College of life Sciences Yantai UniversityYantai 264005China State Key Laboratory of Biobased Material and Green Papermaking Qilu University of Technology(Shandong Academy of Sciences)Jinan 250353China

Directed evolution(DE)inspired by natural evolution(NE)has been achieving tremendous successes in protein/enzyme ***,the conventional"one-protein-for-one-task"DE cannot match the"multi-proteins-for-multi-tasks"NE in terms of screening throughput and efficiency,thus often failing to meet the fast-growing demands for biocatalysts with desired *** this study,we design a novel"multi-enzymes-for-multi-substrates"(MEMS)DE model and establish the proof-ofconcept by running a NE-mimicking and higher-throughput screening on the basis of"two-P450 s-against-seven-substrates"(2P×7S)in one *** the multiplied throughput and improved hit rate,we witness a series of convergent evolution events of the two archetypal cytochrome P450 enzymes(P450 BM3 and P450 cam)in *** is anticipated that the new strategy of MEMS DE will find broader application for a larger repertoire of enzymes in the ***,structural and substrate docking analysis of the two functionally convergent P450 variants provide important insights into how distinct P450 active-sites can reach a common catalytic goal.

关键词： MEMS directed evolution cytochrome P450 enzymes high-throughput screening convergent evolution ambroxide 3β-hydroxylase

Functional expression and regulation of eukaryotic cytochrome P450 enzymes in surrogate microbial cell factories

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Engineering Microbiology 2022年第1期2卷 17-34页

作者： Pradeepraj Durairaj shengying li State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266237ShandongChina Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237ShandongChina

Cytochrome P450(CYP)enzymes play crucial roles during the evolution and diversification of ancestral monocel-lular eukaryotes into multicellular eukaryotic organisms due to their essential functionalities including catalysis of housekeeping biochemical reactions,synthesis of diverse metabolites,detoxification of xenobiotics,and con-tribution to environmental *** CYPs with versatile functionalities are undeniably regarded as promising biocatalysts with great potential for biotechnological,pharmaceutical and chemical industry ***,the modes of action and the challenges associated with these membrane-bound proteins have hampered the effective utilization of eukaryotic CYPs in a broader *** review is focused on comprehen-sive and consolidated approaches to address the core challenges in heterologous expression of membrane-bound eukaryotic CYPs in different surrogate microbial cell factories,aiming to provide key insights for better studies and applications of diverse eukaryotic CYPs in the *** also highlight the functional significance of the previously underrated cytochrome P450 reductases(CPRs)and provide a rational justification on the progression of CPR from auxiliary redox partner to function modulator in CYP catalysis.

关键词： Cytochrome P450 enzymes Cytochrome P450 reductase Membrane-bound proteins N-terminal transmembrane domain Heterologous expression Microbial cell factories Redox partners Electron transfer

COX-2 blocking therapy in cisplatin chemosensitization of ovarian cancer:An allicin-based nanomedicine approach

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Chinese Chemical Letters 2024年第8期35卷 449-454页

作者： Huijiao Fu Peiqin liang Qianwen Chen Yan Wang Guang li Xuzi Cai Shengtao Wang Kun Chen shengying Shi Zhiqiang Yu Xuefeng Wang Department of Obstetrics and Gynecology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China Department of Obstetrics and Gynecology Huizhou Central People’s HospitalHuizhou 516001China Affiliated Foshan Maternity&Child Healthcare Hospital Southern Medical University(Foshan Maternity&Child Healthcare Hospital)Foshan 528000China Guangdong Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Nursing Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Laboratory Medicine Dongguan Institute of Clinical Cancer ResearchThe Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital)Dongguan 523018China

Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably ***,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting ***,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive *** one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP ***,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA *** essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.

关键词： COX-2 blocking therapy CDDP Chemosensitization Allicin Ovarian cancer