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Genome-Based Metabolic Engineering of Mannheimia succiniciproducens for Succinic Acid Produ

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A PPLIED AND E NVIRONMENTAL M ICROBIOLOGY,Mar.2006,p.1939–1948Vol.72,No.3 0099-2240/06/$08.00ϩ0doi:10.1128/AEM.72.3.1939–1948.2006Copyright©2006,American Society for Microbiology.All Rights Reserved.Genome-Based Metabolic Engineering of Mannheimia succiniciproducensfor Succinic Acid Production‡Sang Jun Lee,1,2†Hyohak Song,1†and Sang Yup Lee1,2,3*Metabolic and Biomolecular Engineering National Research Laboratory,Department of Chemical and Biomolecular Engineering,1 Center for Ultramicrochemical Process Systems,2and Department of BioSystems,BioProcess Engineering Research Center and Bioinformatics Research Center,3Korea Advanced Institute of Science and Technology,373-1Guseong-dong,Yuseong-gu,Daejeon305-701,Republic of KoreaReceived7November2005/Accepted3January2006Succinic acid is a four-carbon dicarboxylic acid produced as one of the fermentation products of anaerobicmetabolism.Based on the complete genome sequence of a capnophilic succinic acid-producing rumen bacte-rium,Mannheimia succiniciproducens,gene knockout studies were carried out to understand its anaerobicfermentative metabolism and consequently to develop a metabolically engineered strain capable of producingsuccinic acid without by-product formation.Among three different CO2-fixing metabolic reactions catalyzed byphosphoenolpyruvate(PEP)carboxykinase,PEP carboxylase,and malic enzyme,PEP carboxykinase was the most important for the anaerobic growth of M.succiniciproducens and succinic acid production.Oxaloacetate formed by carboxylation of PEP was found to be converted to succinic acid by three sequential reactions catalyzed by malate dehydrogenase,fumarase,and fumarate reductase.Major metabolic pathways leading to by-product formation were successfully removed by disrupting the ldhA,pflB,pta,and ackA genes.This metabolically engineered LPK7strain was able to produce13.4g/liter of succinic acid from20g/liter glucose with little or no formation of acetic,formic,and lactic acids,resulting in a succinic acid yield of0.97mol succinic acid per mol glucose.Fed-batch culture of M.succiniciproducens LPK7with intermittent glucose feeding allowed the production of52.4g/liter of succinic acid,with a succinic acid yield of1.16mol succinic acid per mol glucose and a succinic acid productivity of1.8g/liter/h,which should be useful for industrial production of succinic acid.Succinic acid,also known as butanedioic or amber acid,is afour-carbon dicarboxylic acid synthesized as an intermediate ofthe tricarboxylic acid cycle and also as one of the mixed-acidfermentation products.There is growing interest in the pro-duction of succinic acid from renewable resources by microbialfermentation because succinic acid can be used in numerousapplications(36,37).Some anaerobic bacteria,such as Anaero-biospirillum succiniciproducens(6)and Actinobacillus succino-genes(10),produce succinic acid as a major fermentation prod-uct of their metabolism.During anaerobic fermentation,thegreenhouse gas CO2isfixed by carboxylation reactions,con-verting C3to C4metabolites.Although A.succiniciproducensand A.succinogenes are able to produce relatively more suc-cinic acid than other microorganisms,concomitant production of metabolic by-products,such as acetic,formic,and lactic acids,is problematic because it reduces the succinic acid yield and makes the purification process difficult and costly.With an aim to reduce by-product formation,several differ-ent approaches have been taken.In one example,Guettler et al.(9)developed a monofluoroacetate-resistant mutant strain of A.succinogenes that produced less acetic and formic acids than the parent strain.In other studies,Lee et ed glycerol as a carbon source(22)and supplied hydrogen gas(21)duringfermentation to reduce by-product formation and simulta-neously enhance succinic acid production by A.succiniciprodu-cens.However,production of mixed acids still persisted. Succinic acid production by recombinant Escherichia coli has also been intensively studied in the last decade(5,12–14,31, 34).Successful metabolic engineering of E.coli resulted in substantial increases in the succinic acid yield and productivity (5,12,13,24,28,31,34,35).Vemuri et al.(35)reported an impressive result,achieving99g/liter of succinate by fed-batch fermentation of recombinant E.coli.However,relatively large amounts of acetic acid and ethanol were concomitantly pro-duced,which is a problem to be solved.Recently,a gram-negative capnophilic bacterium,Mannheimia succiniciproducens MBEL55E,was isolated from the rumens of Korean cows(20).M.succiniciproducens was able to produce a large amount of succinic acid as a major fermentation product under anaerobic conditions in the presence of CO2.More re-cently,we reported the complete genome sequence of M.succi-niciproducens and in silico genome scale metabolic characteristics (11).The genome scale metabolic-flux analysis showed that phos-phoenolpyruvate(PEP)carboxylation is a major CO2-fixing step (Fig.1),and thisflux has a direct relationship with succinic acid flux in a branched tricarboxylic acid cycle(11).Having the com-plete genome sequence of M.succiniciproducens in hand,we examined the possibility of eliminating the by-product formation by metabolic engineering.Here,we report the strategies for the metabolic engineering of M.succiniciproducens based on the ge-nome sequence and construction of an improved succinic acid producer with reduced by-product formation.*Corresponding author.Mailing address:Department of Chemical and Biomolecular Engineering,Korea Advanced Institute of Science and Technology,373-1Guseong-dong,Yuseong-gu,Daejeon305-701, Republic of Korea.Phone:82428693930.Fax:82428693910.E-mail: leesy@kaist.ac.kr.†These authors contributed equally to this work.‡Supplemental material for this article can be found at http://aem/.1939MATERIALS AND METHODSStrains and media.All strains and plasmids used in this study are listed in Table 1.E.coli was cultivated in Luria-Bertani (LB)medium (10g/liter Bacto tryptone,5g/liter yeast extract,and 10g/liter sodium chloride)at 37°C.M.succiniciproducens MBEL55E (KCTC 0769BP;Korean Collection for Type Cultures,Daejeon,Korea)was routinely cultivated in LB medium supplemented with 10g/liter of glucose at 37°C.Batch fermentations were carried out at 39°C(see below).When needed,chloramphenicol (Cm),kanamycin (Km),and spec-tinomycin (Sp)were added at concentrations of 34,25,and 50␮g/ml,respec-tively,for E .coli and 6.8,25,and 50␮g/ml,respectively,for M.succiniciprodu-cens .Plasmids.All restriction enzymes used in this work were purchased from New England Biolabs (Ipswich,MA).Ex Taq DNA polymerase (Takara,Shiga,Japan)was used for PCR.Genomic DNA was isolated from M.succiniciproducensFIG.1.Central fermentative metabolic pathways leading to the formation of mixed acids in M .succiniciproducens MBEL55E (solid arrows).The dashed arrows and parentheses indicate metabolic pathways and isoenzyme genes,respectively,which are not found in M .succiniciproducens but are found in E.coli K-12(see Table S1in the supplemental material).The filled circles indicate the genes disrupted for the characterization of metabolic-flux redistribution and the construction of a succinic acid overproducer.The boldface arrows indicate major metabolic pathways leading to succinic acid formation in M .succiniciproducens .TABLE 1.Bacterial strains and plasmids used in this studyStrain or plasmidRelevant characteristicsReference or sourceM.succiniciproducens MBEL55E Bovine rumen isolate 20M.succiniciproducens LK ldhA ::Km rThis study M.succiniciproducens LPK ldhA ::Km r pflB ::Cm rThis study M.succiniciproducens LPK2ldhA ::Km r pflB ::Cm r pckA ::Sp r This study M.succiniciproducens LPK4ldhA ::Km r pflB ::Cm r ppc ::Sp r This study M.succiniciproducens LPK5ldhA ::Km r pflB ::Cm r maeB ::Sp r This study M.succiniciproducens LPK6ldhA ::Km r pflB ::Cm r fumC ::Sp rThis study M.succiniciproducens LPK7ldhA ::Km r pflB ::Cm r pta-ackA ::Sp r This study E.coli XL1-Blue Cloning hostStratagenepUC18 2.7kb;Ap r ;cloning vector New England Biolabs pUC19 2.7kb;Ap r ;cloning vectorNew England Biolabs pACYC184 4.2kb;Cm r Tet r ;chloramphenicol resistance gene New England Biolabs pUC4K 4.0kb;Ap r Km r ;kanamycin resistance gene Pharmacia pKmobsacB 5.7kb;Km r sacB ;levansucrase gene29pIC1564.0kb;Sp r ;spectinomycin resistance gene 30pLDHK-sacB 7.8kb;Ap r Km r sacB ;ldhA disruption vector This study pPFLC-sacB 8.0kb;Ap r Cm r sacB ;pflB disruption vector This study pPPCS-sacB 7.8kb;Ap r Sp r sacB ;ppc disruption vector This study pPCKS-sacB 7.8kb;Ap r Sp r sacB ;pckA disruption vector This study pMAES-sacB 8.0kb;Ap r Sp r sacB ;maeB disruption vector This study pFUMS-sacB 7.8kb;Ap r Sp r sacB ;fumC disruption vectorThis study pPTAS-sacB8.0kb;Ap r Sp r sacB ;pta and ackA gene disruption vector This study1940LEE ET AL.A PPL .E NVIRON .M ICROBIOL .MBEL55E using a Wizard Genomic DNA Purification Kit(Promega,Madison, WI).The oligonucleotides used in this study are listed in Table2.An ldhA gene disruption vector containing two homologous regions was constructed as follows.PCR was performed with oligonucleotide primers P1and P2using the genomic DNA of M.succiniciproducens as a template.The PCR product was digested with SacI and PstI and ligated into the SacI-PstI-digested pUC18to make pLDH1(see Fig.S1in the supplemental material).Similarly, the PCR product obtained with primers P3and P4was digested with PstI and HindIII and ligated into the PstI-HindIII-digested pLDH1to make pLDH12. The PstI-digested Km resistance gene cassette from pUC4K was inserted into the PstI-digested pLDH12to make pLDH1K2.Linker P5was inserted into SacI-digested pLDH1K2to make a new XbaI site in the plasmid.To amplify the sacB gene,PCR was carried out using pKmobsacB(29)as a template and the oligonucleotide primers P6and P7.Finally,the PCR product was digested with XbaI and inserted into the XbaI site of pLDH1K2to make pLDHK-sacB for knocking out the ldhA gene(see Fig.S1in the supplemental material). To make a pflB gene disruption plasmid,the sacB gene was amplified with primers P8and P9,digested with PstI and BamHI,and ligated into the PstI-BamHI-digested pUC19to make pUC19-sacB.PCR was performed with primers P10and P11using the genomic DNA of M.succiniciproducens as a template.TheTABLE2.Oligonucleotides used in this studyName Sequence(5Ј33Ј)a CommentsP1CAGTGAAGGAGCTCCGTAACGCATCCGCCG SacIP2CTTTATCGAATCTGCAGGCGGTTTCCAAAA PstIP3GTACTGTAAACTGCAGCTTTCATAGTTAGC PstIP4GCCGAAAGTCAAGCTTGCCGTCGTTTAGTG HindIIIP5TCTAGAAGCT XbaIP6GCTCTAGACCTTCTATCGCCTTCTTGACG XbaIP7GCTCTAGAGGCTACAAAATCACGGGCGTC XbaIP8AGCGGATCCCCTTCTATCGCCTTCTTGACG BamHIP9GTCCTGCAGGGCTACAAAATCACGGGCGTC PstIP10CATGGCGGATCCAGGTACGCTGATTTCGAT BamHIP11CAAGGATCCAACGGATAAAGCTTTTATTAT BamHIP12CTCGAGCCCGGGGTTTAAGGGCACCAATAA SmaIP13CTCGAGCCCCGGGCTTTGCGCCGAATAAAT SmaIP14TACGGATCCCCAGAAAATCGCCCCCATGCCGA BamHIP15GCTCTAGATATCGTTTGATATTGTTCCGCCACATTTG XbaI,EcoRVP16CGGGATCCGATATAAAGCGATGTTCTTGCTTGCCCAAT BamHIP17GCTCTAGATATCATTATTGGAAAATATATGAAAATAA XbaI,EcoRVP18CGGGATCCACCTGCAGATCACGGGCAATATTC BamHIP19GCTCTAGATATCATAATTTTAGTAGCGAATTCCGGCTGCG XbaI,EcoRVP20GCTCTAGATATCGACAAATGGGTGGTACCTGCCGATATGG XbaI,EcoRVP21GTGGTGGATCCTAAACGTTCCGAAGCCTTGTTATCC BamHIP22GCTCTAGATATCCGCAGTATCACTTTCTGCGC XbaI,EcoRVP23TCCGCAGTCGGATCCGGGTTAACCGCACAG BamHIP24GCTCTAGATATCCGTCAGGAAAGCACCCGCCATAGC XbaI,EcoRVP25GGGGAGCTCGTGTGGCGCTGCGGAAGTAAGGCACAAAATC SacIP26GCTCTAGATATCTATGGCGCTATCAAACGTGA XbaI,EcoRVP27GGGGAGCTCATTTGTTATACAGATTAAATAATTTTTGCC SacIP28GCTCTAGATATCCGACTACAATCAACGAAGAAATGAAAATG XbaI,EcoRVP29GGGGAGCTCACGCCACTTGCGGTTCAATACCGAAACGG SacIP30CCAGTCCATACCGATTTCCTGTGCGAGCTC SacIP31GCTCTAGATATCTGCAGGAACCTGCACTTCACCCATAG XbaI,EcoRVP32GGGGAGCTCGCTAACTTAGCTTCTAAAGGCCATGTTTCC SacIP33GCTCTAGATATCCGGGTCAATATCGCCGCAAC XbaI,EcoRVP34GCTCGCCCGGGGATCGATCCTCTAGAGT SmaIP35CCCCCCCGGGCCGACAGGCTTTGAAGCATG SmaIP36GACGTTTCCCGTTGAATATGGC KmR5ЈendP37CATTGAGGCGTATTATCAGGAAAC ldhA upstreamP38GCAGTTTCATTTGATGCTCGATG KmR3ЈendP39CCTCTTACGATGACGCATCTTTCC ldhA downstreamP40GGTGGTATATCCAGTGATTTTTTTCTCCAT CmR5ЈendP41CTTTGCAACATTATGGTATGTATTGCCG pflB upstreamP42TACTGCGATGAGTGGCAGGGCGGGGCGTAA CmR3ЈendP43CCCCAGCATGTGCAAATCTTCGTCAC pflB downstreamP44TCAAATTGCTCATGATTTCACCTCGTTG SpR5ЈendP45GATCCAGGGAATGGCACGCAGGCTTTCAACGCCGCC ppc upstreamP46GGCTATCGGGGAGAGTGTGATGATAAGTGG SpR3ЈendP47GCAAAGCCAGAGGAATGGATGCCATTAACCAATAGCG ppc downstreamP48GGCGTATTTCAGGCAGACGTAGGCGATGCAACCGAC pckA upstreamP49GCTTTACCGCCATCTTGGACTAAGGTTGCGGCAAG pckA downstreamP50GAGCAGATTTGCCGCGCCTTTGAGCGGACTGTCAGGC maeB upstreamP51GGTTTGCGCCCGTAGCTATCGCCCACCGGTCCCCAG maeB downstreamP52CGATACCCTGTGCCGCTCGTGCCGAAAGCTTGGCGG fumC upstreamP53GCGGTGTAGGTTTGGGCGGTTATTGGGCTGAGCGGG fumC downstreamP54GCTGCCAAACAACCGAAAATACCGCAATAAACGGC pta-ackA upstreamP55GCAACGCGAGGGTCAATACCGAAGGATTTCGCCG pta-ackA downstream a Restriction sites are underlined.V OL.72,2006SUCCINIC ACID PRODUCTION BY ENGINEERED MANNHEIMIA1941PCR product was digested with BamHI and ligated into the BamHI-digested pUC19-sacB to make pPFL12-sacB.To amplify a Cm resistance gene,PCR was performed with primers P12and P13using pACYC184as a template.The SmaI-digested Cm resistance gene cassette was ligated into the Bst1107I-di-gested pPFL12-sacB to make pPFLC-sacB(see Fig.S2in the supplemental material).To make the ppc,pckA,maeB,fumC,and pta-ackA gene disruption vectors,PCRs were performed with the primer pairs P14-P15,P16-P17,P18-P19, P20-P21,and P22-P23,respectively,using the genomic DNA of M.succinici-producens as a template.The PCR products were subsequently digested with XbaI and BamHI and cloned into the XbaI-BamHI sites of pUC19to make pPPC1,pPCK1,pMAE1,pFUM1,and pPTA1,respectively.Then,PCR prod-ucts obtained with primer pairs P24-P25,P26-P27,P28-P29,P30-P31,and P32-P33were digested with XbaI and SacI and cloned into the XbaI-SacI sites of pPPC1,pPCK1,pMAE1,pFUM1,and pPTA1to make pPPC12,pPCK12, pMAE12,pFUM12,and pPTA12,respectively.The Sp resistance gene cassette was amplified from pIC156(30)using primers P34and P35,digested with SmaI, and inserted into the EcoRV sites of pPPC12,pPCK12,pMAE12,pFUM12,and pPTA12to make pPPC1S2,pPCK1S2,pMAE1S2,pFUM1S2,and pPTA1S2, respectively.The orientation of Sp resistance genes in these plasmids was con-firmed by PCR.Finally,the SacI-BamHI-digested DNA fragments of pPPC1S2, pPCK1S2,pMAE1S2,pFUM1S2,and pPTA1S2were cloned into the SacI-BamHI sites of pUC19-sacB to make pPPCS-sacB,pPCKS-sacB,pMAES-sacB, pFUMS-sacB,and pPTAS-sacB,respectively(see Fig.S2in the supplemental material).Gene knockouts.M.succiniciproducens MBEL55E was grown to an optical density at600nm(OD600)of0.25.Cells from100ml of broth were harvested and washed twice with cold10%(vol/vol)glycerol solution and resuspended in1ml of10%(vol/vol)glycerol petent cells(50␮l)were mixed with10␮l of plasmid DNA(5␮g/␮l)isolated from E.coli XL1-Blue.Electroporation was performed using a Gene Pulser(Bio-Rad,Hercules,CA;1.8kV,200⍀,and25␮F)and a0.1-cm electrode gap cuvette(Bio-Rad).After incubation in1ml of LB broth containing10g/liter glucose at37°C for1.5h,the cells were spread on an LB agar plate containing10g/liter glucose and25mg/liter of Km,6.8mg/liter of Cm,or50mg/liter of Sp,depending on the suicide vector employed.After incubation at37°C for48h,transformants were randomly selected and trans-ferred twice onto an LB agar plate containing100g/liter of sucrose and antibi-otics as indicated above.Finally,several candidates were grown in LB medium containing10g/liter glucose,and their genomic DNAs were isolated for the confirmation of gene inactivation as follows.Disruption of the ldhA gene by double crossover was confirmed by PCRs using primer pairs P36-P37and P38-P39.Primers P37and P39are located outside the cloned sequence in the pLDHK-sacB vector,and primers P36and P38are located in the Km resistance gene.Inactivation of the pflB gene by allelic exchange was confirmed by PCRs using primer pairs P40-P41and P42-P43.Primers P41and P43are located outside the cloned sequence in the pPFLC-sacB vector,and primers P40and P42 are located in the Cm resistance gene.Similarly,inactivation of the ppc,pckA, maeB,fumC,and pta-ackA genes was confirmed by PCRs using primer pairs P44-P45and P46-P47,P44-P48and P46-P49,P44-P50and P46-P51,P44-P52and P46-P53,and P44-P54and P46-P55,respectively(Table1).Fermentation.M.succiniciproducens cells were routinely cultivated anaerobi-cally in sealed bottles containing250ml of MH3medium plus5g/liter of glucose and1mg/ml of Na2S·9H2O under a CO2atmosphere.MH3medium contains (per liter)2.5g polypeptone,2.5g yeast extract,3g K2HPO4,1g NaCl,1g (NH4)2SO4,0.2g CaCl2·2H2O,0.2g MgCl2·6H2O,and3g MgCO3.Batch cultures were carried out in a6.6-liter Bioflo3000fermentor(New Brunswick Scientific Co.,Edison,NJ)containing2.25liters of modified MH3(MMH3) medium plus20g/liter glucose.MMH3medium contains(per liter)5g yeast extract,1.25g NaCl,0.4g CaCl2·2H2O,0.4g MgCl2·6H2O,5.02g K2HPO4, and2.87g KH2PO4.Fermentations were carried out at the optimal temperature of39°C as reported previously(20).The pH was adjusted to6.5using28% (vol/vol)ammonia solution.Foaming was controlled by the addition of Antifoam 289(Sigma,St.Louis,MO).CO2gas,scrubbed free of oxygen by passing it through an oxygen trap(Agilent,Waldbronn,Germany),was sparged through-out the fermentation at aflow rate of0.25vol/vol/min.Agitation speed was controlled at200rpm.Fed-batch culture was carried out under the same con-ditions as batch cultures,using MMH3medium containing63g/liter of glucose.A concentrated solution containing700g/liter glucose and20g/liter MgSO4·7H2O was fed into the fermentor using a peristaltic pump(Cole-Parmer,Vernon Hills,IL)when the glucose concentration in the fermentor decreased to ca.30 g/liter,in order to maintain the glucose concentration at30to45g/liter. Analytical procedures.The concentrations of glucose and organic acids were determined by high-performance liquid chromatography(ProStar210;Varian, Palo Alto,CA)equipped with UV/visible-light(ProStar320;Varian,Palo Alto,CA)and refractive index(Shodex RI-71,Tokyo,Japan)detectors.A MetaCarb 87H column(300by7.8mm;Varian)was eluted isocratically with0.01N H2SO4 at60°C at aflow rate of0.6ml/min.Cell growth was monitored by measuring the OD600using an Ultrospec3000spectrophotometer(Pharmacia Biotech,Upp-sala,Sweden).The cell concentration,defined as grams dry cell weight per liter, was calculated from the predetermined standard curve relating the OD600to dry weight(an OD600of1ϭ0.451g dry cell weight/liter).RESULTSDevelopment of the gene knockout method.Since appropri-ate genetic tools and plasmid vectors for engineering M.suc-ciniciproducens were not available,wefirst developed a gene knockout ing pUC19as a backbone plasmid,sui-cide vectors having the sacB gene,which has been used as a counterselectable marker(26)in many gram-negative bacteria and several gram-positive Corynebacterium species,were con-structed to completely remove the functional open reading frames of the genes of interest from the chromosome.The strategy employed for inactivating the ldhA and pflB genes,as examples,is depicted in Fig.2.After the transforma-tion of the plasmid pLDHK-sacB,cells that integrated the plasmid into the chromosome by single crossover were selected in a medium containing Km and glucose.Two types of inte-gration,upstream and downstream of the ldhA gene,are pos-sible,as shown in Fig.2.Among the cells with thefirst cross-over,those that lost the ldhA gene by the second crossover were selected in a medium containing Km and sucrose.Wild-type M. succiniciproducens has an invertase gene and can utilize su-crose as a carbon source.However,recombinant cells with the sacB gene cannot survive on high-sucrose medium,due to the accumulation of a levan polymer synthesized from sucrose by a levansucrase(encoded by the sacB gene).Cells that failed to remove the gene replacement plasmid containing the sacB gene by double crossover lysed on the agar plate containing a high concentration of sucrose.The candidates with the ldhA gene disrupted were confirmed by PCRs using two primer pairs,P36-P37and P38-P39.For the further inactivation of the pflB gene,the LK strain with the ldhA gene disrupted was transformed with pPFLC-sacB.Cells harboring the plasmid in their chromosome by thefirst crossover were selected in a medium containing Cm and glucose.Cells with the second crossover were selected in a medium containing Cm and sucrose.The candidates with pflB inactivated were confirmed by PCRs using two oligo-nucleotide pairs,P40-P41and P42-P43.As a result,the LPK strain with ldhA-pflB disrupted was constructed.From this LPK strain,LPK2,LPK4,LPK5,LPK6,and LPK7strains were similarly constructed using plasmids pPCKS-sacB, pPPCS-sacB,pMAES-sacB,pFUMS-sacB,and pPTAS-sacB, respectively.The respective transformants were selected in a medium containing Sp and glucose for thefirst crossover,fol-lowed by selection for the second crossover in a medium con-taining Sp and sucrose.Thefinal knockout candidates were confirmed by PCRs using the primer sets listed in Table2(see also Materials and Methods).Effects of disrupting the ldhA and pflB genes.The genes responsible for the formation of acetic,formic,lactic,and succinic acids in M.succiniciproducens MBEL55E were se-1942LEE ET AL.A PPL.E NVIRON.M ICROBIOL.FIG.2.Strategies for disrupting the ldhA and pflB genes in the chromosome of M.succiniproducens MBEL55E by using the integrative plasmids pLDHK-sacB and pPFLC-sacB,which contain the counterselectable levansucrase gene (sacB ).V OL .72,2006SUCCINIC ACID PRODUCTION BY ENGINEERED MANNHEIMIA 1943lected from a functionally annotated genome database (15).The genes coding for the enzymes involved in the mixed-acid fermentative metabolism of M.succiniciproducens were com-pared with the known genes of E.coli K-12(see Table S1in the supplemental material).The key enzymes present in E .coli ,but not in M .succiniciproducens ,include a glucose-specific phosphotransferase system (PTS),NAD ϩ-dependent malic enzyme,membrane-associated malate dehydrogenase,fuma-rases A and B,pyruvate kinase I,pyruvate oxidase,and acetyl-coenzyme A synthetase (see Table S1in the supplemental material).Our recent study suggested that M.succiniciprodu-cens does not utilize the PTS for glucose uptake;rather,it possesses a glucokinase activity to transfer phosphate from ATP to glucose (23).The metabolic pathways leading to the formation of succinic acid and other organic acids in M.suc-ciniciproducens under anaerobic condition are shown in Fig.1.Batch cultivation of wild-type M.succiniciproducens in MMH3medium containing 22.5g/liter glucose resulted in the production of 10.5g/liter succinic acid,4.96g/liter acetic acid,4.10g/liter formic acid,and 3.47g/liter lactic acid (Fig.3A).In order to eliminate the formation of by-products,the genes responsible for the formation of acetic,formic,and lactic acids were sequentially knocked out.First,the ldhA gene was dis-rupted to prevent lactic acid formation.Anaerobic fermenta-tion of the ldhA -deficient M .succiniciproducens LK strain showed much less lactic acid formation.Concomitantly,the final succinic acid concentration and yield increased to 12.0g/liter and 0.90mol succinic acid per mol glucose (Fig.3B).Next,the pflB gene was additionally inactivated with an aim to eliminate the formation of acetic and formic acids.The forma-tion of formic acid was completely eliminated (Fig.3C).Pro-duction of acetic acid was significantly reduced in the LPK strain but still persisted.This suggests that there are other metabolic pathways contributing to the formation of acetic acid.Due to the inactivation of the major pyruvate dissimila-tion pathways and limited reducing power in the LPK strain,3.26g/liter of pyruvic acid and 1.95g/liter of malic acid were produced.Also,the specific growth rate of the LPK strain (0.33h Ϫ1)was lower than those of the wild-type strain (0.88h Ϫ1)and the LK strain (0.59h Ϫ1).Nonetheless,it is notable that succinic acid formation increased to a final con-centration of 13.4g/liter with no formic acid and much less lactic acid production as a result of the ldhA and pflB inacti-vation (Fig.3C).The succinic acid yield was 0.97mol succinic acid per mol glucose (0.63g succinic acid per g glucose).Comparison of three CO 2-fixing pathways.Since succinic acid is a four-carbon dicarboxylic acid,carboxylation of PEP or pyruvate is an important step in its production.Three enzymes,PEP carboxylase (ppc )(18),PEP carboxykinase (pckA )(7),and malic enzyme (maeB )(4,17),were considered to be re-sponsible for the carboxylation of PEP or pyruvate in M .succiniciproducens .To examine which enzyme plays the most important role in C 3-C 4conversion,the maeB ,ppc ,and pckA genes of M .succiniciproducens were separately disrupted intheFIG.3.Fermentation profiles of M .succiniciproducens MBEL55E (A),the LK strain with ldhA disrupted (B),the LPK strain with ldhA-pflB disrupted (C),and the LPK7strain with ldhA-pflB-pta-ackA disrupted (D).},cell growth;F ,glucose;E ,succinic acid; ,lactic acid;‚,formic acid;■,acetic acid;छ,malic acid;ᮀ,pyruvic acid.DCW,dry cell weight.1944LEE ET AL.A PPL .E NVIRON .M ICROBIOL .LPK strain.The LPK5strain with ldhA -pflB -maeB inactivated showed fermentation patterns similar to that of its parent LPK strain (Fig.3C and 4A).The LPK4strain with ldhA -pflB -ppc inactivated also showed a fermentation profile (Fig.4B)similar to those of the LPK and LPK5strains,except that it consumed glucose much more rapidly and produced more pyruvate (3.79g/liter)and less acetic acid (1.36g/liter).On the other hand,the LPK2strain with ldhA -pflB -pckA inactivated showed very slow growth during the entire period of anaerobic fermenta-tion,resulting in a significant decrease in succinic acid produc-tivity (Fig.4C and Table 3).These observations suggest that PEP carboxykinase encoded by the pckA gene plays the most important role in both anaerobic growth of M .succiniciprodu-cens and efficient succinic acid production.Furthermore,the LPK6strain,which is the LPK strain with fumC inactivated,could not grow under anaerobic conditions (data not shown),which suggests that formation of succinic acid is essential for the growth of the M.succiniciproducens LPK strain under an-aerobic conditions.To our knowledge,this is the first report to present direct experimental evidence that the carbon flux effi-ciently flows from PEP to succinic acid via oxaloacetate,malate,and fumarate by metabolic pathways comprised of PEP carboxykinase,malate dehydrogenase,fumarase,and fumarate reductase in anaerobic succinic acid fermentation (Fig.1).Reducing acetic acid production.Inactivation of the ldhA and pflB genes almost completely blocked the formation of lactic and formic acids,but not acetic acid.With an aim to eliminate acetic acid formation,presumably contributed by unknown metabolic pathways,two key enzymes,phosphotrans-acetylase and acetate kinase,were further inactivated in the LPK strain to make the LPK7strain.Acetic acid production was almost completely blocked in the LPK7strain (Fig.3D).The mass ratio of succinic acid to acetic acid and the succinic acid yield on glucose at the end of fermentation were 11.98-and 1.42-fold,respectively,higher than those obtained with a wild-type strain (Table 4).However,cell growth was somewhat negatively affected,presumably due to the shortage of ATP,which otherwise could be supplied by an acetate kinase reac-tion (Fig.1).As observed with the LPK strain,pyruvic and malic acids were accumulated during the fermentation of the LPK7strain,reaching 2.47and 2.62g/liter,respectively,at the end of fermentation (Table 4).They were not further con-verted to succinic acid even after prolonged fermentation (data not shown).Fed-batch fermentation.Fed-batch fermentation of the M .succiniciproducens LPK7strain was performed toachieveFIG.4.Fermentation profiles of the ldhA-pflB -disrupted M.succi-niciproducens mutant strains LPK5(A),LPK4(B),and LPK2(C),which additionally lack the CO 2-fixing maeB ,ppc ,and pckA genes,respectively.},cell growth;F ,glucose;E ,succinic acid; ,lactic acid;‚,formic acid;■,acetic acid;छ,malic acid;ᮀ,pyruvic acid.DCW,dry cell weight.TABLE 3.Effects of disruption of major CO 2-fixing enzymes in succinic acid fermentation by M.succiniciproducensStrainConcn of fermentation products (g/liter [mM])Specific growth rate (h Ϫ1)Maximum volumetricsuccinic acid productivity (g/liter/h)Succinic acidAcetic acidFormic acidLactic acidMalic acidPyruvic acidLPK 13.42(113.63) 2.06(34.30)ND a 0.37(4.05) 1.95(14.54) 3.26(36.97)0.33 1.59LPK2 5.74(48.57) 1.32(21.98)ND 0.30(3.33)0.60(4.48) 1.02(11.58)0.040.11LPK411.77(99.68)0.74(12.35)ND0.19(2.09) 2.55(19.02) 4.83(54.87)0.40 1.98LPK511.72(99.25) 1.36(22.68)0.09(1.89)0.29(3.23) 2.12(15.84) 3.79(43.00)0.38 1.48aND,not detected.V OL .72,2006SUCCINIC ACID PRODUCTION BY ENGINEERED MANNHEIMIA 1945。

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野生型菌种驯化方法

野生型菌种驯化方法

野生型菌种驯化方法引言野生型菌种的驯化是微生物研究领域的重要课题之一。

驯化过程能够使菌种产生更多有益的化合物，并提高其产量和稳定性。

本文将探讨野生型菌种的驯化方法。

传统驯化方法选择合适的菌种在驯化菌种之前，首先需要选择合适的菌种作为研究对象。

一般来说，菌种应具有较高的生物活性和代谢能力。

通过筛选野生菌库，挑选出对所需化合物具有潜在生产能力的菌株。

优化培养基将选定的菌株进行培养需要提供适宜的培养基。

不同菌种对培养基的需求不同，可以通过改变培养基的成分、浓度和pH值等参数，以获得更适合菌株生长和产物积累的培养条件。

适应性培养适应性培养是驯化菌种的重要步骤。

将选定菌株分次接种入含有目标化合物的培养基中，逐渐增加其浓度，让菌株适应并逐渐提高对该化合物的产生能力。

遗传改造传统驯化方法还包括遗传改造。

通过利用基因工程技术，对菌株进行基因的插入、删除或突变，以改变菌株的代谢途径和产物合成能力。

经过反复筛选和遗传改造，可以获得更高产和更稳定的驯化菌株。

现代驯化方法基因组学驯化随着高通量测序技术的发展，基因组学在菌种驯化中发挥了重要作用。

通过对野生菌株的基因组进行测序，可以揭示其代谢途径和可能的产物合成能力。

基于这些信息，可以有针对性地进行菌株的驯化和优化。

代谢工程代谢工程是现代驯化方法中的重要手段。

通过构建合成生物学工具箱，可以对菌株进行精细的代谢工程调控。

例如，通过调节关键代谢途径的酶活性和基因表达水平，可以增加目标产物的合成通路和产量。

体内进化体内进化是一种新兴的菌种驯化方法。

通过在宿主动物或植物内部进行反复驯化，可以利用宿主环境的选择压力产生菌株的进化变异。

这种方法可以快速筛选出适应宿主环境和具有高产能力的驯化菌株。

基于人工智能的驯化近年来，人工智能在驯化菌种中的应用也越来越广泛。

通过机器学习和数据挖掘等技术，可以分析大量的菌株信息和产物数据，快速发现驯化菌株的关键特征和优化策略。

结论野生型菌种的驯化是微生物研究的重要课题之一。

河南省创新发展联盟2024-2025学年高三上学期9月月考英语试题

河南省创新发展联盟2024-2025学年高三上学期9月月考英语试题

河南省创新发展联盟2024-2025学年高三上学期9月月考英语试题一、阅读理解Join a Zion National Park ranger (护林人) to learn about what makes Zion National Park unique. Programs are free and created for classrooms and individuals. We connect to your school or home through a free web-based program. You will be provided with a link to the video conference ahead of time via an email invite. Registration is open! Click on the program below for more information. Program 1—Chat with a RangerIn Chat with a Ranger, students learn about Zion National Park, the park service, and the life of a ranger. Students prepare and send questions ahead of time. This program can be adapted to fit different curriculum objectives, and is appropriate for any age group. Program 2—Pollination InvestigationIn this distance learning program, students will discover what pollination is and how important it is to all ecosystems. Looking at the relationship between plants and pollinators, participants will see how they have influenced each other and will be challenged to create their own perfect pollinator. Program 3—Whooo’s in the Canyon?Who left these clues behind here in the high canyons of Zion National Park? A feather, small bones, and hoot hooting in the trees can be heard as your classroom goes on a virtual hike of Zion to discover the Mexican spotted owl. Learn it about how the owl uses its special adaptations to survive in this desert environment. Program 4—The Forests, Wetlands, and Deserts of Zion This distance learning program focuses on the plants and animals that live in Zion's varying ecosystems. Students will learn about their adaptations and relationships to each other in this interactive lesson with a creative and critical thinking activity.1．Which program requires participants to make preparations in advance?A．Chat with a Ranger.B．Pollination Investigation.C．Whooo's in the Canyon?D．The Forests, Wetlands, and Deserts of Zion. 2．What can participants learn from program 3?A．Survival strategies taken by owls in the park.B．Ways to prepare a hike tour in the park.C．Threats brought by the desert environment.D．A variety of ecosystems in ZionNational Park.3．What do the listed programs have in common?A．They involve interactive activities.B．They include a virtual tour of different trails.C．They are accessible through web-based program.D．They require participants to visit the park in person.On a hot June day in 2015, I retired after 34 years of teaching high school. Then, I drove to meet my new piano teacher, Mark.I had worked for more than three decades as a busy English teacher with an endless stream of papers to mark and precious little time to experiment or learn new skills. I was determined to make up for all I had been missing. I wanted to finally master the piano and learn how to make music.I told Mark I had a specific concrete goal: to play Clair de lune by Claude Debussy, a piece I remember hearing from early childhood.Determined that there would be a day when I would totally master this piece, I set myself a deadline: I would perform before a gathering of friends on my 60th birthday. For months I did nothing but furiously (猛烈地) practise. When the day came, around 30 friends and relatives crowded into my dining room to hear me play, and aside from a few minor slips, I managed to pull it off without embarrassing myself. People clapped warmly. I made it. I had risen to a challenge, but I still didn’t feel that I was really “making music”.After that, my progress was painfully slow. I had come to hate hearing myself play music badly. I got no pleasure from the act of missing notes.I began focusing on what few things I could do: gardening and cycling. I came to understand that I didn’t have to be that man I’d always thought I ought to be. I could just do what feels good. So, after nearly five years of lessons, I quit.I still love music; I regularly go out to concerts. But now my piano does nothing more than sit silently in my dining room, displaying family photos and collecting dust. And I’m perfectly happy with that.4．Why did the author learn the piano after retiring from teaching?A．To impress his friends and relatives.B．To avoid the boredom of retirement.C．To start a new career as a concert pianist.D．To pursue a long-time passion for music. 5．What can be inferred from paragraph 4?A．The author attended a concert of piano music.B．The author performed successfully despite a few errors.C．The author felt embarrassed about his piano performance.D．The author quit his piano immediately after his 60th birthday.6．What does the author do with his piano now?A．He uses it for music lessons.B．He uses it for performance.C．He uses it for something unrelated to music.D．He plays it for personal enjoyment occasionally.7．Which of the following can best describe the author?A．Inner- directed and hardworking.B．Conventional and careless.C．Ambitious and kind-hearted.D．Lazy and pessimistic.When it comes to diatoms (硅藻类) that live in the ocean, new research suggests that photosynthesis (光合作用) is not the only strategy for accumulating carbon. Instead, these single-celled are also building biomass by feeding directly on organic carbon in the ocean.These new findings could lead researchers to reduce their estimate of how much carbon dioxide diatoms pull out of the air via photosynthesis, which in turn, could take a much closer look at the understanding of the global carbon cycle, which is especially relevant given the changing climate. The new findings were published in Science Advances on July 17, 2024.The team showed that the diatom Cylindrotheca closterium, which is found in oceans around the world, regularly performs a mix of both photosynthesis and direct eating of carbon from organic sources such as plankton (浮游生物) . In more than 70% of the water samples the researchers analyzed from oceans around the world, the team found signs of simultaneous photosynthesis and direct organic carbon consumption from Cylindrotheca closterium. The team also showed that this diatom species can grow much faster when consuming organic carbon in addition to photosynthesis. Furthermore, the new research hinted at the possibility that specificspecies of bacteria are feeding organic carbon directly to a large percentage of these diatoms living all across the global ocean. This work is based on a genome-scale metabolic modeling approach that the team used to reveal the metabolism of the diatom Cylindrotheca closterium.The team’s new metabolic modeling data support recent lab experiments suggesting that some diatoms may rely on strategies other than photosynthesis to intake the carbon they need to survive, thrive and build biomass.The UC San Diego led team is in the process of expanding the scope of the project to determine how widespread this non-photosynthetic activity is among other diatom species. 8．What’s new according to the research?A．The way of the diatom’s carbon accumulation.B．The impact of climate on diverse sea plants.C．The procedure of exploring carbon.D．The system of building biomass.9．What do the new findings make researchers more focus on?A．The causes of climate change.B．The grasp of the carbon cycle.C．The bad effect of photosynthesis on diatoms.D．A rough estimate of the amount of carbon dioxide.10．What do we know from paragraph 3?A．A large number of diatoms may feed on bacteria.B．The diatom lives on plankton.C．Water samples are key factors for the research.D．Diatom species grow faster with sufficient sunlight11．Which is the most suitable title for the text?A．Photosynthesis in Diatoms B．Plankton’s Role in OceansC．New Carbon Strategies in Diatoms D．Advances in Modeling DataAccording to a report in 2023, the World Health Organization (WHO) recommended that non-sugar sweeteners not be used as a means of achieving weight control or reducing the risk of diseases. The guideline came as a surprise. After all, the very purpose of non-sugar sweeteners-which contain little to no calories—is to help consumers control their weight and reduce their risk of disease by replacing sugar.In its report, the WHO cited evidence that long-term use of non-sugar sweeteners is associated with an increased risk of diabetes (糖尿病) and death. How is it that non-sugar sweeteners are linked to the negative health effects they’re supposed to fend off?The WHO made its recommendation after reviewing hundreds of published studies. The problem is that the overwhelming majority of these studies are observational. In such studies, subjects tend to self-report their food intake, which might not guarantee inaccuracy. More importantly, observational studies cannot determine cause and effect. Are non-sugar sweeteners causing diabetes, or are people at risk of diabetes simply more likely to consume them? Lastly, there are numerous variables that researchers can’t possibly control for in these studies that could influence the results.Randomized controlled trials (RCTs) tell a different story about non-sugar sweeteners. These studies control for variables by randomly assigning people to either a treatment or control group, and they can determine cause and effect. They show that sweeteners modestly benefit weight loss and help control blood sugar, without the negative effects seen in observational research. The downside of RCTs is that they are shorter in duration, often lasting just a few months. So negative effects could appear after longer use and we wouldn’t be able to tell from these RCTs.But we also can’t tell from observational studies, which only measure correlation and not causality (因果关系) . Changing the current situation might be hard, though. RCTs are expensive and require recruiting participants, setting up diet plans, and regularly measuring subjects’ health outcomes.For change to happen, it might need to start at the top, where science is funded Government agencies, which appropriate billions for research, should start prioritizing RCTs.12．What do the underlined phrase “fend off” probably mean in paragraph 2?A．Put out.B．Defend against.C．Keep up.D．Count on. 13．What does paragraph 3 mainly talk about?A．The WHO’s suggestions on observational studies.B．The strategies to decide cause and effect in conducting studies.C．The significance of controlling variables in observational studies.D．The limitations of the observational studies in the WHO report.14．What is a feature of RCTs according to the text?A．They cost little B．They tend to last long.C．They can control variables and determine causality.D．They require participants to self-report related data15．How should the government help RCTs?A．By making appropriate plans B．By providing financial supportC．By raising people’s awareness of health D．By founding more related governmentagenciesTo make science’s stories more concrete and engaging, it’s important to use some effective strategies. Here are four of them. Put people in the storyScience’s stories often lack human characters. 16 . Characters can be also people affected by a scientific topic, or interested in learning more about it. Besides, they can be storytellers who are sharing their personal experiences.17People often think of science as objective and fair. But science is actually a human practice that continuously involves choices, missteps and biases (偏见) . If you explain science as a course, you can walk people through the sequence of how science is done and why researchers reach certain conclusions. 18 . And they can also stress the reason why people should trust the course of science to provide the most accurate conclusions possible given the available information. Include what people care aboutScientific topics are important, but they may not always be the public’s most pressing concerns. In April 2024, a polling company found that “the quality of the environment” was one of thelowest-ranked priorities among people in the US. The stories about the environment could weave in connections to higher-priority topics. 19 . Tell science's storiesScientists, of course, can be science communicators, but everyone can tell science’s stories. When we share information online about health, or talk to friends and family about the weather, we contribute to information that circulates about science topics. 20 . Think about all of a story’s characteristics - character, action, sequence, scope, storyteller and content - and how you might incorporate them into the topic.A．Explain science as a processB．Shoot attractive short science videosC．Scientists themselves can actually become ideal onesD．This practice is to stress why the content is importantE．You can tell growth stories of remarkable teenage scientistsF．Science communicators can emphasize how science is conductedG．You may as well borrow features from stories to strengthen your message二、完形填空In 2018, Molly Baker unfortunately lost her husband in a severe skiing accident. She was 21 . In the first several weeks after his passing, her friends and family 22 a great deal of support. But after a while, the cards and meals started to 23 . “People had to get back to their normal 24 . And so things kind of dropped off,” Baker recalled.That was when one of Baker's friends, Carla Vail, thought up a way to 25 the help for an entire year. She called it the “Calendar Girls”. V ail gathered the names of 31 of Baker's friends who wanted to help, and 26 each friend a particular day. Vail also gave Baker the names on the 27 , so Baker could know what to 28 each day.“And what that looked like for them was that on that day, they would reach out to me in some 29 ways—maybe via text, or a card,” Baker said.Looking back, Baker feels that Vail's 30 was essential to helping her cope with her husband's death, because she was 31 at that time.“A lot of people are really uncomfortable around 32 ,” Baker said. “So what they do is, instead of doing something, that they 33 do nothing. It was nice to have that ‘Calendar Girls’ setup.”Today, Baker tries to do something similar for her friends going through 34 . In hard times, she knows how 35 it is to have something to look forward to every day. 21．A．cautious B．unconscious C．desperate D．impassive 22．A．extended B．demanded C．announced D．assumed 23．A．pass down B．show up C．break up D．slow down24．A．exercise B．routine C．diet D．growth 25．A．resist B．continue C．explain D．test 26．A．ordered B．sent C．owed D．assigned 27．A．furniture B．file C．calendar D．Internet 28．A．expect B．absorb C．propose D．define 29．A．rare B．strange C．specific D．generous 30．A．curiosity B．thoughtfulness C．ambition D．toughness 31．A．innocent B．optimistic C．tolerant D．lonely 32．A．panic B．evidence C．failure D．grief 33．A．simply B．hardly C．skillfully D．secretly 34．A．distraction B．addiction C．loss D．annoyance 35．A．amusing B．valuable C．astonishing D．universal三、语法填空阅读下面短文，在空白处填入1个适当的单词或括号内单词的正确形式。

医学细胞生物学英文词汇翻译

医学细胞生物学英文词汇翻译

医学细胞生物学英文词汇翻译Prepared on 21 November 2021医学细胞生物学专业英语词汇acrocentricchromosome近端着丝粒染色体actin肌动蛋白actinfilament肌动蛋白丝actinomycinD放线菌素Dactivator活化物activetransport主动运输adenine腺嘌呤adenosinemonophosphate,AMP腺苷一磷酸,腺苷酸adenylcyclase,AC腺苷酸环化酶adhesionplaque黏着斑agranularendoplasmicreticulum无颗粒内质网Alzheimerdisease阿尔茨海默病aminoacid氨基酸aminoacylsite,Asite氨基酰位，A位amitosis;directdivision无丝分裂；直接分裂amphipathicmolecule双型性分子anaphase后期anchoringjunction锚定连接annulargranule孔环颗粒anticodingstrand反编码链antigen抗原antiparallel逆平行性apopticbody凋亡小体apoptosis凋亡assembly组装aster星体asymmetry不对称性autolysis自溶作用autophagolysosome自噬性溶酶体autophagy自噬作用autoradiography放射自显影技术autosome常染色体Blymphocyte B淋巴细胞bacteria细菌basesubstitution碱基替换beltdesmosome带状桥粒bioblast生命小体biologicalmacromolecule生物大分子biomembrane生物膜biotechnology生物技术bivalent二价体breakage断裂cadherin钙粘连素calmodulin,CaM钙调蛋白cAMP环一磷酸腺苷cAMP-dependentproteinkinase环一磷酸腺苷依赖型蛋白激酶capping戴帽carrierprotein载体蛋白catcrysyndrome猫叫综合症celldivisioncyclegene CDC基因cell细胞cellandmolecularbiology细胞分子生物学cellbiology细胞生物学cellcoat;glycocalyx细胞衣；糖萼cellculture细胞培养cellcycle细胞周期cellcycle-regulatingprotein细胞周期调节蛋白cellcycletime细胞周期时间celldetermination细胞决定celldifferentiation细胞分化celldivisioncycle,CDC细胞分裂周期celldivisioncyclegene,CDCgene细胞分裂周期基因cellengineering细胞工程cellfractionation细胞分级分离cellfusion细胞融合celljunction细胞连接cellline细胞系cellmembrane;plasmamembrane细胞膜；质膜cellplate细胞板cellproliferation细胞增殖cellrecognition细胞识别cellsurfaceantigen细胞表面抗原celltheory细胞学说cellstrain细胞株cellaging细胞衰老cellsynchronization细胞同步化cellularoxidation细胞氧化cellularrespiration细胞呼吸centralgranule中央颗粒centromere着丝粒chalone抑素channelprotein通道蛋白chemiosmotichypothesis化学渗透假说chiasmata交叉cholesterol胆固醇chromatid染色单体chromatin染色质chromomere染色粒chromosome染色体chromosomearm染色体臂chromosomebanding染色体带chromosomedisease染色体病chromosomeengineering染色体工程chromosomescaffold染色体支架chromosomesyndrome染色体综合症cisGolginetworkcisterna（pl.cisternae）顺面高尔基网状结构扁平囊clathrin笼蛋白clone克隆coatedpit有被小窝coatedvesicle包被小泡codingstrand编码链codon密码子codondegeneracy密码子兼并性coenzyme辅酶collagenfibronectin,FN纤连蛋白communicationjunction通讯连接complementation互补性condensationstage凝集期confocallaserscanningmicroscope共焦激光扫描显微镜connexin连接子constitutiveheterochromatin结构异染色质continuousmicrotubules极微管convertingenzyme转变酶crista（pl.cristae）嵴cyanine 胞嘧啶cyclin细胞周期素cydoeximide放线菌酮cytidinemonophosphate,CMP胞苷一磷酸，胞苷酸cytokinesis细胞质分裂cytology细胞学cytoplasm细胞质cytoplasmengineering细胞质工程cytoplasmsubstitution细胞质代换cytoplasmicplaque胞质斑cytoskeleton细胞骨架darkfieldmicroscope暗视野显微镜dedifferentiation去分化degeneracy兼并deletion缺失densitygradientcentrifugation密度梯度离心deoxyadenosinemonophosphate,dAMP脱氧腺苷酸deoxycytidinemonophosphate,dCMP脱氧胞苷酸deoxyguanosinemonophosphate,dGMP脱氧鸟苷酸deoxyribonucleicacid,DNA脱氧核糖核酸deoxythymidinemonophosphate,dTMP脱氧胸苷酸desmosome桥粒diakinesis终变期differentialcentrifugation差速离心differentialexpression差异性表达differentiationinduction分化诱导differentiationinhibition分化抑制diplococcuspneumonia肺炎双球菌diplotene双线期disassembly去组装DNAprobe DNA探针DNAsynthesisphase DNA合成期dosagecompensation剂量补偿doublet二联管duplication重复effector效应器electriccoupling电偶联electronmicroscope电子显微镜elementaryparticle基粒eletronfusion电融合elongationfactor,EF延长因子embryonicinduction胚胎诱导作用endocytosis内吞作用endolysosome内体性溶酶体endomembranesystem内膜系统endoplasmicreticulum,ER内质网enhancer增强子enzyme酶equatorialplane赤道面eucaryotes真核生物euchromatin常染色质eukaryoticcell真核细胞exocytosis胞吐作用exon外显子extracellularmatrix,ECM细胞外基质extrinsic;peripheralprotein外在蛋白；外周蛋白Fbody荧光小体facilitateddiffusion易化扩散facultativeheterochromatin兼性异染色质fibrillarcomponent原纤维成分fibronectin,FN纤粘连蛋白fibrousactin,F-actin纤维状肌动蛋白flankingsequence侧翼顺序fluidmosaicmodel液态镶嵌模型fluorescencemicroscope荧光显微镜荧光漂白恢复fluorescencerecoveryafterphotobleaching,FRAPfork-initiationprotein叉起始蛋白frameshiftmutation移码突变freecell游离细胞freediffusion自由扩散freeenergy自由能galactocerebroside半乳糖脑苷脂ganglioside神经节苷脂gapjunction间隙连接gene基因genecluster基因簇geneengineering基因工程geneexpression基因表达genefamily基因家族genemutation基因突变geneticcode遗传密码geneticmessage遗传信息genome基因组genomeengineering染色体工程genomicDNAlibrary基因组DNA文库glycogenstoragediseasetypeⅡⅡ型糖原蓄积病glycolipid糖脂glycoprotein糖蛋白glycosaminoglycan,GAG氨基聚糖glycosylation糖基化Golgiapparatus高尔基器Golgibody高尔基体Golgicomplex高尔基复合体granularcomponent颗粒成分granulardrop脱粒granularendoplasmicreticulum颗粒内质网growthfactor生长因子GT-AGrule GT-AG法则guanine鸟嘌呤guanosinemonophosphate,GMP鸟苷一磷酸，鸟苷酸hemidesmosome半桥粒hereditaryfactor遗传因子heterochromatin异染色质heterogeneousnuclearRNA,hnRNA不均一核RNA heterokaryon异核体heterophagolysosome异噬性溶酶体heterophagy异噬作用heteropyknosis异固缩highlyrepetitivesequence高度重复序列histone组蛋白holoenzyme全酶homokaryon同核体housekeepinggene管家基因housekeepingprotein管家蛋白humanleukocyteantigen,HLA人白细胞抗原hyaluronicacid,HA透明质酸hybridcell杂交细胞hyperdiploid超二倍体hypodiploid亚二倍体immunofluorescencemicroscopy免疫荧光显微镜技术immunoglobulin免疫球蛋白invitro离体的invivo体内的inactiveXhypothesis失活X假说inbornerrorsofmetabolism先天性代谢缺陷病inducer诱导物induction诱导inhibitorofmitoticfactor,IMF有丝分裂因子抑制物initiationfactor,IF起始因子innermembrane内膜innernuclearmembrane内层核膜insertionsequence,IS插入顺序Integralprotein整合蛋白integrin整连蛋白intermembranespace;outerchamber膜间腔；外室intercellularcommunication细胞间通讯intercristalspace;innerchamber嵴间腔；内室intermediatefilament中间纤维internalmembrane内膜internalreticularapparatus内网器interphase间期interstitialdeletion中间缺失interzonalmicrotubules区间微管intracristalspace嵴内腔intra-nucleolarchromatin核仁内染色质intrinsic;integralprotein内在蛋白；整合蛋白intron内含子inversion倒位invertedrepetitivesequence倒位重复顺序ionicchannel离子通道ioniccoupling离子偶联jumpinggene跳跃基因karyotype核型kinetochore着丝点kinetochoremicrotubules动粒微管Klinefelter’ssyndrome先天性睾丸发育不全症laggingstrand后随链laminin,LN层粘连蛋白lateraldiffusion侧向扩散leadingstrand前导链leptotene细线期ligand;chemicalsignal配体；化学信号lightmicroscope光学显微镜linearpolymer线性多聚体linker连接线liposome脂质体liquidcrystal液晶lowdensitylipoprotein,LDL低密度脂蛋白luxurygene奢侈基因luxuryprotein奢侈蛋白lymphokine淋巴激活素lymphotoxin淋巴毒素lysosome溶酶体majorhistocompatibilitycomplex,MHC组织相容性复合体malignancy恶性matricalgranule基质颗粒matrix基质matrixfibronectin,mFN基质纤连蛋白maturation-promptingfactor,MPF成熟促进因子medialGolgistack高尔基中间囊膜meiosis减数分裂membraneantigen膜抗原membranecarbohydrate膜碳水化合物membraneflow膜流membranelipid膜脂membraneprotein膜蛋白membranereceptor膜受体membranousstructure膜相结构messengerRNA信使核糖核酸mesosome中间体metaboliccoupling代谢偶联metacentricchromosome中央着丝粒染色体metaphase中期micelle微团microfilament微丝microscopy显微镜技术microsome微粒体microtrabecularlattice微梁网格microtubule微管microtubuleassociatedprotein,MAP微管结合蛋白microtubuleorganizingcenters,MTOC微管组织中心microvillus微绒毛middlerepetitivesequence中度重复序列miniband微带missensemutation错义突变mitochondria线粒体mitosis有丝分裂mitosisphase有丝分裂期mitoticapparatus有丝分裂器mitoticfactor,MF有丝分裂因子mobility流动性modelforcontrollinggeneexpression基因表达调控模型molecularbiology分子生物学moleculardisease分子病monopotentcell单能细胞monosomy单体性multiplecoilingmodel多级螺旋模型multipotentcell多能细胞myastheniagravis重症肌无力症mycoplasma支原体myofibrils肌原纤维necrosis坏死neuropeptide神经肽non-continuation不连续性non-histone非组蛋白non-membranousstructure非膜相结构nonsensemutation无义突变nuclearenvelope核被膜nuclearlamina核纤层nuclearmatrix核基质nuclearpore核孔nuclearporecomplex核孔复合体nuclearsap核液nuclearsex核性别nuclearskeleton核骨架nucleicacid核酸nucleicacidhybridization核酸分子杂交nucleo-cytoplasmicratio核质比nucleoid类核体nucleoids拟核nucleolarassociatedchromatin核仁相随染色质nucleolarorganizingregion核仁组织区nucleolus核仁nucleosome核小体nucleotide核苷酸nucleosomecore核小体核心nucleus细胞核nucleustransplantation核移植法nucleus-cytoplasmhybrid核质杂种Okazakifragment岗崎片段oligomerfibronectin,oFN寡聚纤连蛋白oncogene癌基因operatorgene操纵基因operon操纵子operontheory操纵子学说organelle细胞器origin起点outermembrane外膜outernuclearmembrane外层核膜overlappinggene重叠基因oxidativephosphorylation氧化磷酸化pachytene粗线期pairingstage配对期partialmonosome部分单体partialtrisomy部分三体passivetransport被动运输patching成斑现象peptidebond肽键peptidylsite,Psite肽基位；P位perinuclearspace核间隙perinucleolarchromatin核仁周围染色质peripheralgranule周边颗粒peripheralprotein外周蛋白permeability通透性peroxisome;microbody过氧化物酶体；微体phagocytosis吞噬作用phagolysosome吞噬性溶酶体phagosome自噬体phasecontrastmicroscope相差显微镜phenylalaninehydroxylase,PAH苯丙氨酸羟化酶phenylketonuria,PKU苯丙酮尿症phosphatidylinositol,PL磷脂酰肌醇phosphodiesterbond磷酸二酯键phosphodiesterase,PDE磷酸二酯酶phosphoglyceride磷酸甘油酯phospholipaseC,PLC磷脂酶C phospholipid磷脂pinocytosis胞饮作用pinocytoticvesicle吞饮泡plasmacell浆细胞plasmafibronectin,pFN血浆纤连蛋白plasmid质粒pointmutation点突变polarmicrotubule极间微管polarizingmicroscope偏光显微镜polyadenylation多聚腺苷酸反应polyploid多倍体polyribosome多聚核糖体prematurecondensedchromosome,PCC早熟染色体premeiosisinterphase减数分裂前间期primaryconstriction主缢痕primaryculture原代培养primaryculturecell原代细胞programmedcelldeath细胞程序性死亡prokaryotes原核生物prokaryoticcell原核细胞promotor启动子promotorgene启动基因prophase前期protein蛋白质proteinkinaseC,PKC蛋白激酶C proteoglycan,PG蛋白聚糖protofilament原纤维protooncogene原癌基因protoplasm原生质purine嘌呤碱pyrimidine嘧啶碱receptormediatedendocytosis受体介导的内吞作用reciprocaltranslocation相互易位recombinantDNAtechnology重组DNA技术recombinationnodules重组小节recombinationstage重组期recondensationstage再凝集期redifferentiation再分化regulatorgene调节基因releasefactor,RF释放因子replication复制replicationeyes复制眼replicationfork复制叉replicon复制子repressor阻碍物resolvingpower分辨力residualbody残体respiratorychain呼吸链restrictionendonuclease限制性内切核酸酶restrictionpoint限制点reversetranscription逆转录rhofactor,ρρ因子ribonucleicacid,RNA核糖核酸ribophorin核糖体结合蛋白ribosomalRNA核糖体核糖核酸ribosome核糖核蛋白体RNApolymerase RNA聚合酶roughendoplasmicreticulum,rER sac 粗面内质网扁平囊samesensemutation同义突变sarcoplasmicreticulum肌质网satellite随体scanningelectronmicroscope扫描电子显微镜scanningtunnelingmicroscope扫描隧道电子显微镜secondaryconstriction次缢痕secondaryculture传代培养semiautonomousorganelle半自主性的细胞器semiconservativereplication半保留复制semidiscontinuousreplication半不连续复制sensor感受器sequentialexpression顺序表达sexchromosome性染色体signalcodon信号密码子signalhypothesis信号肽假说signalmolecule信号分子signalpeptide信号肽signalrecognitionparticle,SPR信号识别颗粒simplediffusion简单扩散singlesequence单一序列single-strandedDNAbindingprotein单链DNA结合蛋白singlet单管smallnuclearRNA,snRNA小分子细胞核RNA smoothendoplasmicreticulum,sER滑面内质网solenoid螺线管sparsomycin稀疏酶素sphingomyelin神经鞘磷脂spindle纺锤体splicing剪接splitgene断裂基因startcodon起始密码子stemcell干细胞stressfiber张力基因structuralgene结构基因submetacentricchromosome亚中着丝粒染色体supersolenoid超螺线管suppressortRNA校正tRNAsynapsis联会synaptonemalcomplex联会复合体synkaryon合核体synonymouscodon同义密码子synonymousmutation同义突变Tlymphocyte T淋巴细胞tailing加尾telomere端粒telophase末期terminaldeletion末端缺失terminalization端化terminator终止子tetrad四分体tetraploid四倍体thymine胸腺嘧啶threedimensionalstructure,3D三维结构tightjunction紧密连接tissuecell组织细胞tissueengineering组织工程totipotency全能性transGolginetwork反面高尔基网状结构transcribedspacer转录间隔区transcription转录transdifferentiation转分化transferRNA转运核糖核酸transformation转化transition转换translation翻译translocation易位transportprotein运输蛋白transposition转座transversion颠换transmissionelectronmicroscope透视电子显微镜tricarboxylicacidcycle三羧酸循环triggerprotein触发蛋白triplet三联管triploid三倍体triskelion三臂蛋白trisomy三体tubulin微管蛋白tumornecrosisfactor肿瘤坏死因子Turner’ssyndrome先天性卵巢发育不全症tyrosinase,TN酪氨酸酶ultravoltageelectronmicroscope超高压电子显微镜unitmembrane单位膜untranscribedspacer非转录间隔区unwindingprotein解链蛋白uracil尿嘧啶uridinemonophosphate,UMP vacuole 尿苷一磷酸；尿苷酸大囊泡vector载体vesicle小囊泡vinculin粘着斑连接蛋白wobblehypothesis摇摆学说Xchromatin X染色质Ychromatin Y染色质zygotene偶线期麻醉学PublicHealth公共健康Cancer/Oncology癌症/肿瘤PulmonaryDisease肺脏疾病CardiacElectrophysiology心脏电生理Radiation辐射病学Cardiology-Interventional心脏病-介入Radiology放射病学Cardiology-Noninvasive心脏病-无创介入ReproductiveEndocrinology生殖内分泌病学CardiologyandCirculation 心脏与循环系统疾病Respiratory呼吸科ClinicalGenetics临床遗传学Rheumatology风湿病学ClinicalImmunology临床免疫学Stomatology口腔医学clinicallaboratory检验科SexualDysfunction性功能障碍医学ClinicalPharmacology临床药理学SpinalCordInjury脊髓损伤病学ClinicalPsychology临床心理学Surgery-General普通外科CriticalCareMedicine 危重病医学Toxicology毒理学Dentistry牙科Urology泌尿科Dermatology皮肤科VeterinaryScience兽医学Dermatopathology皮肤病理学Virology病毒学Diabetes糖尿病OccupationalMedicine职业医学EmergencyMedicine 急诊医学Oncology-Medical 肿瘤医学Endocrinology内分泌医学Oncology-Radiation 放射肿瘤学Epidemiology流行病学Oncology-Surgical 肿瘤外科手术学FamilyPractice家庭实践医学Ophthalmology眼科Gastroenterology 胃肠病学Orthopedics骨科学Geriatrics老年病学OtherClinicalMedicine 其他临床医学Gynecology妇产科学Otorhinolaryngology 耳鼻咽喉科Hematology血液学PainMedicine疼痛医学Hematology-Oncology 血液肿瘤学PalliativeMedicine姑息医学Hepatology肝脏病学Pathology病理学Hypertension高血压Pediatrics小儿科InfectiousDiseases传染病学PhysicalMedicine&Rehab 理疗与康复InternalMedicine内科学Physiology生理学Maternal&FetalMedicine 孕产妇和胎儿医学plasticsurgery整形外科Microbiology微生物学PreventiveMedicine预防医学Nephrology肾脏病学Psychiatry精神病学Neurology神经病学Psychiatry-Addiction 精神病学-成瘾学Neurology-Child儿童神经病学Psychiatry-Child精神病学-儿童NuclearMedicine核医学Psychiatry-General精神病学-一般Nursing护理学Psychiatry-Geriatric 精神病学-老年Nutrition营养学Pharmacology药理学Obstetrics&Gynecology 妇产科学PlantScience植物科学OccupationalMedicine职业医学Zoology动物学麻醉学PublicHealth公共健康Cancer/Oncology癌症/肿瘤PulmonaryDisease肺脏疾病CardiacElectrophysiology 心脏电生理Radiation辐射病学Cardiology-Interventional 心脏病-介入Radiology放射病学Cardiology-Noninvasive心脏病-无创介入ReproductiveEndocrinology生殖内分泌病学CardiologyandCirculation 心脏与循环系统疾病Respiratory呼吸科ClinicalGenetics临床遗传学Rheumatology风湿病学ClinicalImmunology临床免疫学Stomatology口腔医学clinicallaboratory检验科SexualDysfunction性功能障碍医学ClinicalPharmacology临床药理学SpinalCordInjury脊髓损伤病学ClinicalPsychology临床心理学Surgery-General普通外科CriticalCareMedicine 危重病医学Toxicology毒理学Dentistry牙科Urology泌尿科Dermatology皮肤科VeterinaryScience兽医学Dermatopathology皮肤病理学Virology病毒学Diabetes糖尿病OccupationalMedicine职业医学EmergencyMedicine 急诊医学Oncology-Medical 肿瘤医学Endocrinology内分泌医学Oncology-Radiation 放射肿瘤学Epidemiology流行病学Oncology-Surgical 肿瘤外科手术学FamilyPractice家庭实践医学Ophthalmology眼科Gastroenterology 胃肠病学Orthopedics骨科学Geriatrics老年病学OtherClinicalMedicine 其他临床医学Gynecology妇产科学Otorhinolaryngology 耳鼻咽喉科Hematology血液学PainMedicine疼痛医学Hematology-Oncology 血液肿瘤学PalliativeMedicine姑息医学Hepatology肝脏病学Pathology病理学Hypertension高血压Pediatrics小儿科InfectiousDiseases传染病学PhysicalMedicine&Rehab 理疗与康复InternalMedicine内科学Physiology生理学Maternal&FetalMedicine 孕产妇和胎儿医学plasticsurgery整形外科Microbiology微生物学PreventiveMedicine预防医学Nephrology肾脏病学Psychiatry精神病学Neurology神经病学Psychiatry-Addiction 精神病学-成瘾学Neurology-Child儿童神经病学Psychiatry-Child精神病学-儿童NuclearMedicine核医学Psychiatry-General精神病学-一般Nursing护理学Psychiatry-Geriatric 精神病学-老年Nutrition营养学Pharmacology药理学Obstetrics&Gynecology 妇产科学PlantScience植物科学OccupationalMedicine 职业医学Zoology动物学s。

生物反应器工程国家重点实验室-华东理工大学

生物反应器工程国家重点实验室-华东理工大学

2010年学术活动第169次SKLBE学术论坛作者：管理员发布：2010年12月16日浏览次数: 172报告人：中国科学技术大学生命科学学院合肥微尺度物质科学国家实验室（筹）刘海燕教授报告题目：分子间相互作用的再造与合成生物学元件摘要：合成生物学的重要理念之一是用模块化、标准化的单元构建有功能的生物系统。

在生物系统中，不同单元之间的“接口”主要需通过分子间相互作用实现，相互作用的特异性决定了不同“接口”之间的绝缘性。

由于生物大分子序列、结构和功能具有模块化的特点，通过分子间相互作用的设计和再造可作为一种通用的元件设计策略，包括：通过对酶-底物结合特异性的改造获得新的催化分子；通过对信号传导分子间结合特异性的改造改变信号通路、通过再造蛋白质-DNA、小分子-RNA相互作用获得通用的转录调控元件等。

本文将结合我们在计算方法、人工转录元件设计方面的工作讨论蛋白质参与的分子间相互作用再造。

时间：2010-12-16 下午2∶00地点：实验十八楼315会议室第170次SKLBE学术论坛作者：管理员发布：2010年12月15日浏览次数: 96报告人：复旦大学生科院副院长、复旦大学遗传工程国家重点实验室副主任王红艳教授报告题目：出生缺陷的遗传基础研究时间：2010-12-15下午3∶30地点：实验十八楼315会议室第168次SKLBE学术论坛作者：管理员发布：2010年12月2日浏览次数: 168报告人：生物芯片上海国家工程研究中心副主任张庆华研究员报告题目：蛋白磷酸化抗体芯片技术及在生命科学研究中的应用报告内容：1. 蛋白芯片技术的发展状况 2. 抗体芯片技术应用案例 3. 蛋白磷酸化抗体芯片的技术与产品特点 4. 蛋白与抗体芯片技术的应用与服务时间：2010-12-2 下午3：15地点：实验十八楼315会议室第167次SKLBE学术论坛作者：管理员发布：2010年11月29日浏览次数: 101报告人：日本九州工业大学清水和幸教授(Prof. Kazuyuki Shimizu)题目: Metabolic reguration analysis of a cell focusing on the relationship between global regulators and the metabolic pathway genes together with 13C-metabolic flux analysis时间: 2010年11月29日上午9:00地点: 实验十八楼315室第166次SKLBE学术论坛作者：管理员发布：2010年11月25日浏览次数: 104报告人：华东理工大学资源与环境工程学院危险化学物质风险评价与控制中心教授、博士生导师冯耀宇教授题目: 水回用和水安全—新发水源性病原微生物的检测和污染源追踪时间: 2010年11月25日下午2:00地点: 实验十八楼315室第165次SKLBE学术论坛作者：管理员发布：2010年10月27日浏览次数: 101报告人：Hesham M. Amin, Assiociate Professor, The University of Texas M. D. Anderson Cancer Center, Houston, TX题目: Novel oncogenic systems in lymphoma时间: 2010年10月27日星期三9:30地点: 实验十八楼315室第164次SKLBE学术论坛作者：管理员发布：2010年10月19日浏览次数: 105报告题目：1.含纤维原料制取生物友好型蛋白-糖饲料添加剂2.石油污染土壤生物修复方法,高效应用和反应条件报告人：俄罗斯科学院通讯院士、微生物学家、门捷列夫化工大学生物工程教研组教授妮娜.葛拉朵娃教授时间：2010年10月19上午9:45地点：实验18楼315室第163次SKLBE学术论坛作者：管理员发布：2010年10月18日浏览次数: 103报告题目：嗜热酶结构、功能及分子进化报告人：上海交通大学生命科学技术学院冯雁教授时间：2010年10月18日上午10:30-11:30地点：实验18楼315室第162次SKLBE学术论坛作者：管理员发布：2010年10月18日浏览次数: 119报告题目：Microbial Synthesis of Drugs and Fuels via Synthetic Biology报告人: 美国伊利诺伊大学厄巴纳香槟分校赵惠民教授时间：2010年10月18日上午9:00-10:30地点：实验18楼315第161次SKLBE学术论坛作者：管理员发布：2010年10月16日浏览次数: 106报告题目：Inorganic Surfaces that Selectively Bind Phosphate: Applications in Bioarrays, Biotargeting, and Supported Lipid Bilayers报告人：美国Florida Univeristy化学系主任Dan Talham教授时间：2010年10月16日上午9:30地点：一教101室第160次SKLBE学术论坛作者：管理员发布：2010年10月14日浏览次数: 101报告题目：Growth and Lipidomics Characterization of Nannochloropsis salina for Biofuels报告人：Prof. Peter Lammers, New Mexico State University, USA时间：2010年10月14日上午9:00地点：实验十八楼315室第159次SKLBE学术论坛作者：管理员发布：2010年10月13日浏览次数: 106报告题目：Refining the Vision for Cost-Competive Biofuel Production from Microalgae报告人：Prof. Bryan Willson, Colorado State University, USA时间：2010年10月13日上午9:00地点：实验十八楼315室第158次SKLBE学术论坛作者：管理员发布：2010年9月26日浏览次数: 107报告题目：极端环境微生物资源与利用报告人：浙江大学生命科学学院微生物研究所博士生导师吴敏教授报告时间：2010年9月26日下午2:30地点:实验18楼315室第157次SKLBE学术论坛作者：管理员发布：2010年9月20日浏览次数: 121报告题目：纤维素乙醇糖平台技术的研究进展和展望报告人：山东大学微生物技术国家重点实验室、国家糖工程技术研究中心方诩教授报告时间：2010年9月20日下午2:00地点:实验18楼315室第156次SKLBE学术论坛作者：管理员发布：2010年9月6日浏览次数: 110报告人：我校特聘讲座教授、日本立命馆大学今中忠行教授题目：Application of nano-bubble to biological systems时间：2010年9月6日上午9:00地点：实验十八楼315室第155次SKLBE学术论坛作者：管理员发布：2010年9月1日浏览次数: 93报告人：庞正宇博士，通用电气公司全球研发中心生命科学技术部，高级研究员题目：molecular pathology时间：2010年9月1日下午1:30地点：实验十八楼315室第154次SKLBE学术论坛作者：管理员发布：2010年8月25日浏览次数: 113报告人：Junyong Zhu, Ph.D Scientific Team Leader USDA Forest Products Laboratory题目：Studies on Cellulase Adsorption in Lignocellulosic Suspensions时间：2010年8月25日星期三下午2:00地点：实验十八楼315室第152次SKLBE学术论坛作者：管理员发布：2010年7月23日浏览次数: 106报告人：Dawei Lin, Ph.D. Director, Bioinformatics Core, UC Davis Genome Center题目：Next Generation Biology Through Next Generation Sequencing时间：2010.7.23日(星期五)下午3:00-4:30地点：实验十八楼315室第153次SKLBE学术论坛作者：管理员发布：2010年7月23日浏览次数: 104报告人：国家自然科学基金会审专家、校学位评定委员会委员、生物工程学院院长张元兴教授题目：国家自然科学基金和职称晋升的申请、答辩与评审时间：2010.7.23日(星期五)上午9:00地点：实验十八楼315室第151次SKLBE学术论坛作者：管理员发布：2010年7月21日浏览次数: 120报告人：美国佛罗里达大学化学系V.T and Louis Jackson杰出讲座教授谭蔚泓教授题目：Elucidation of the Molecular Foundation of Cancer:A Chemical Biology Approach时间：2010.7.21日(星期三)下午14:00地点：实验十八楼315室第150次SKLBE学术论坛作者：管理员发布：2010年7月9日浏览次数: 125报告人：华东理工大学药学院杨有军副教授题目： A Highly Selective Low-Background Fluorescent Imaging Agent for NO using Chemodosimeter Involving *in situ* Fluorophore Synthesis (CIFS) Approach时间：2010-7-9(周五)上午9:00地点：实验十八楼315室第149次SKLBE学术论坛作者：管理员发布：2010年7月1日浏览次数: 1811.报告人：Kal Karim 博士，英国克兰菲尔德大学题目：Advancing a healthy life- Education and business activities in Cranfield Health时间：2010-7-1（星期四）上午10:30地点：实验十八楼315室2.报告人：葛屹博士，英国克兰菲尔德大学题目：Exploring unique and holistic solutions to facilitate and promote good health - Cranfield Health’s cuttin g edge researches & technologies时间：2010-7-1（星期四）下午14:00地点：实验十八楼315室3.报告人：李松军博士，英国克兰菲尔德大学题目：智能分子印迹聚合物设计、合成及其可控制、可调节的催化作用时间：2010-7-1（星期四）下午15:30地点：实验十八楼315室第148次SKLBE学术论坛作者：管理员发布：2010年6月29日浏览次数: 122报告人：Dr. Zhen-Yu CHEN (陳振宇教授)Associate Editor, Journal of Agricultural and Food Chemistry题目：How to Write a Manuscript如何撰写高水准的学术论文时间：2010-6-29（星期二）下午2:00地点：实验十八楼315室第147次SKLBE学术论坛作者：管理员发布：2010年6月9日浏览次数: 104报告人: Department of Pharmaceutical Sciences, University of Tennessee Health Science Center Ram I Mahato, PhD题目: Polymeric Nanomedicines and Combination Therapy for treating Prostate Cancer时间: 2010年6月9日星期三下午3:00地点: 实验十八楼315室第146次SKLBE学术论坛作者：管理员发布：2010年6月7日浏览次数: 107报告人:瑞典Attana生物传感器公司高级研究员\生物芯片研发部经理裴志超题目: QCM生物传感器和微阵列技术研究糖-蛋白，蛋白-蛋白相互作用时间:2010年6月7日星期一下午1:30地点:实验十八楼315室第145次SKLBE学术论坛作者：管理员发布：2010年6月1日浏览次数: 107报告人: 中国药科大学化学生物学研究室主任、特聘教授陈依军题目: 诺卡沙星衍生物及其生物合成途径时间: 2010年6月1日星期二下午2:00地点: 实验十八楼315室第144次SKLBE学术论坛作者：管理员发布：2010年5月28日浏览次数: 111报告人: 美国德州农工大学刘文设教授题目: Expanding the Genetic Code时间: 2010年5月28日星期五上午10:00地点: 实验十八楼315室第143次SKLBE学术论坛作者：管理员发布：2010年5月26日浏览次数: 118报告人: 美国弗吉尼亚理工大学、美国能源部生物能源科学中心张以恒教授(我校校友) Y.-H. 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