国家杰出青年基金获得者

国家杰出青年基金获得者 张长生研究员

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时间:2018-01-31  作者:LMB  来源:文本大小:【 |  | 】  【打印

 

 

张长生博士  研究员  

海洋微生物代谢工程与生物合成学科组组长

E-mail: czhang@scsio.ac.cn

   

职务描述

1. 中国科学院南海海洋研究所 所长助理

2. 中国科学院南海海洋研究所 科研规划处处长

3. 中国科学院海洋微生物中心 常务副主任

4. 中国科学院南海海洋研究所研究员,博士生导师

 

研究兴趣与领域

1. 微生物天然活性物质的分离鉴定

2. 复杂微生物次生代谢产物的生物合成研究

3. 微生物次生代谢产物新功能酶的作用机制及其应用  

 

最新研究进展

1. 围绕海洋微生物中大环内酰胺类抗感染、抗肿瘤等药物先导化合物的发现、结构修饰及其生物合成开展研究,主要取得以下两方面的创新性研究成果:

1)为筛选获得更多的PTM产生菌株,对从南海各种海洋生境中分离、鉴定和保藏的海洋放线菌菌株进行筛选,包括设计兼并引物筛选和发酵产物检测。通过PCR筛选从100株放线菌菌株中筛选到10株菌株包含PTM合成相关的基因。通过对4株新的海洋来源链霉菌 Streptomyces sp. JXD1-13Streptomyces sp. JXD1-17Streptomyces sp. JXD3-1Streptomyces sp. JXD50-2进行全基因组扫描序列分析,分别获得了其中的PTM生物合成基因簇,连同之前发现的Streptomyces sp. ZJ306Stretomyces sp. SCSIO 02999Streptomyces albus J1074A. cyanogriseus WH1-2216-6Streptomyces griseus,我们目前共收集到9PTM生物合成基因簇。为获取新的活性优良的PTM类化合物,我们对这4株新的海洋链霉菌进行了小发酵产物检测,发现Streptomyces sp. JXD1-17PTM类化合物产量较高,从以上菌株分离得到了45/5/6型结构的HSAFPTM (暂未发表)。PTM产生菌株和生物合成基因簇的获得为后续开展生物合成机制研究和结构多样化奠定了基础。

2)菌株Streptomyces pactum SCSIO 02999是从南海海域分离鉴定的海洋放线菌,基因组分析发现该基因组中包含一个PTM生物合成基因簇,但在发酵的过程中没有检测到相应产物的存在,表明该基因簇是沉默的。为了解析PTM类化合物的特殊生物合成机制,根据生物信息学分析结果,我们选择对Stretomyces sp. SCSIO 02999PTM生物合成基因簇(命名为Pactamide A)进行深入研究,利用异源表达联合启动子工程的方法,我们成功激活了这条生物合成基因簇。通过体内基因敲除和体外生化等实验探究了pactamide A的生物合成机制,解析了其中三个主要的环化酶功能(PtmB2PtmB1PtmC)。同时,分离鉴定了6个新的、具有癌细胞抑制活性的PTM类化合物1-6命名为pactamides A-FPactamides A-F对四种肿瘤细胞株(SF-268, MCF-7, NCI-H460 Hep-G2) 显示了良好的细胞毒活性(IC50值在0.24 – 26 μM)(Chemical Science 2017, 8, 1607-1612))。发现双功能酶PtmC,既可催化形成5/5/6型成环反应,又可以催化5/6/5型成环反应。 

 

 

2.围绕海洋微生物多环天然产物的发现及其成环机制开展研究, 主要取得如下创新性研究成果: 黄素蛋白在天然产物的生物合成中充当着至关重要的角色,能够催化一系列的生物化学反应。深海来源链霉菌Streptomyces pactum SCSIO 02999中的黄素蛋白XiaK在体内能够将Xiamycin A转化成多个结构奇特的衍生物,包括氯代的CLXM和通过C-NN-N键相连的二聚体DXM A-C。体外酶学实验表明XiaK为氮羟化酶,首先催化Xiamycin A咔唑环上N的羟基化,形成N-hydroxiamycin,该化合物不稳定,能够通过含有自由基的中间体转化为其他的衍生物。这一研究表明非酶催化的反应可能在天然产物的生物合成中起着重要的做用。该结果发表在(Chemical Science 2017, 8(7): 5067-5077),并被Natural products report 作为研究热点报道(Natural Product Reports, 2017, 34 (10): 1180-1184)

 

3.围绕南海来源放线菌次级代谢产物分离鉴定与生物合成研究目标开展了工作, 主要取得如下两方面创新性研究成果:

(1) 从海洋来源的小单孢菌Micromonospora rosaria SCSIO N160中发现了3个含有吡唑环的6/5/6/6/5稠合环系的新骨架结构化合物Pyrazolofluostatin A-C,通过单晶X-ray衍射确定了相关化合物的绝对构型。Pyrazolofluostatin A显示了中等的抗氧化活性(Organic letters 2017, 19, 592-595)。

  

 

(2) 通过灭活两个负调控基因totR3totR5,超量表达正调控基因totR1从海洋来源

Streptomyces pactum SCSIO 02999中激活了一个全长为92KbPKS/NRPS生物合成基因簇,并从中分离到化合物totopotensamides (TPMs) AB和一个新的磺酸化的化合物TPM C。通过体内灭活totG,累积了脱糖的化合物TPM B,表明totG为糖基转移酶;通过体外对totS进行生化实验分析,发现totS可在化合物TPM ADHPG单元上的7位羟基上添加一个磺酸根,生成TPM C,表明totS为磺酸根转移酶,此外totopotensamides生物合成基因簇中还存在多个后修饰酶基因,包括氧化还原酶(totP1totP2totP3totP4,甲基转移酶totM,卤化酶totH等,它们的功能有待进一步研究。这一研究结果发表在 (Organic Letters 2017, 19(20): 5697-5700)杂志上。

  

工作经历

2008.03-至今        中国科学院南海海洋研究所,责任研究员,博士生导师

2006.07-2008.03    美国威斯康星麦迪逊大学药学院,Assistant Scientist,主要从事基于化学-酶法的天然产物结构多样化的新药研发

2003.01-2006.06    美国威斯康星麦迪逊大学药学院,Research Associate,主要从事天然产物的组合生物合成及新颖酶学机制的研究

1998.09-2002.12    德国Wuppertal大学,博士研究生,主要从事微生物次级代谢产物的发现及其组合生物合成研究

1997.07-1998.08    上海太平洋生物高科技有限公司,任助理研究员,主要从事天然产物的发酵工程,活性筛选以及基因工程高产菌的构建

 

教育背景

1998-2002 德国Wuppertal大学化学系,理学博士

1994-1997 华东理工大学生化工程系工学硕士

1990-1994 上海交通大学生物与科学技术系工学学士 

 

获奖与荣誉

1. 2005年获得“First Midwest Carbohydrate Symposium”, Anatrace Best Poster Award

2. 2008年入选中科院引进国外杰出人才(百人计划)(2013年终期评估获得优秀等级)

3. 2011年获得国家杰出青年科学基金(2015年终期评估获得优秀等级)

4. 2012年获得第五届全国优秀科技工作者称号

5. 2014年获得中青年科技创新领军人才称号

6. 2014年入选国家百千万人才工程,获得有突出贡献中青年专家称号

7. 2015年获得广东省培养高层次人才特殊支持计划百千万工程领军人才称号

8. 2015年获得广东省培养高层次人才特殊支持计划杰出人才称号(南粤百杰)

9. 2016年入选国家万人计划科技创新领军人才

10. 2016年国务院特殊津贴获得者

 

学术任职

1. 中国微生物学会海洋微生物学专业委员会、分子微生物学与生物工程专业委员会委员

2. 中国药学会海洋药物专业委员会委员

3.中国生物化学与分子生物学海洋生物化学与分子生物学分会常务理事、副理事长

4. 《热带海洋学报》副主编

5. 《中国海洋药物》编委

6. 《微生物学报》编委

 

 

代表性成果

论文发表: 

2017

1.Subhasish Saha+, Wenjun Zhang+, Guangtao Zhang+, Yiguang Zhu, Yuchan Chen, Qingbo Zhang, Haibo Zhang, Liping Zhang, Weimin Zhang and Changsheng Zhang*,Activation and characterization of a cryptic gene, Chemical Science, 2017,8:1607-1612 

  2. Qingbo Zhang+, Huixian Li+, Lu Yu, Yu Sun, Yiguang Zhu, Hanning Zhu, Liping Zhang, Shu-Ming Li, Yuemao Shen, Changlin Tian, Ang Li, Hung-wen Liu* and Changsheng Zhang*, Characterization of the Flavoenzyme XiaK as an N-Hydroxylase and Implications in Indolosesquiterpene Diversification ,Chemical Science, 2017,8(7):5067-5077

  3. Wenjun Zhang+, Chunfang Yang+, Chunshuai Huang, Liping Zhang, Haibo Zhang, Qingbo Zhang, Chengshan Yuan, Yiguang Zhu, and Changsheng Zhang*,Pyrazolofluostatins A–C, Pyrazole-Fused Benzo[a]fluorenes from South China Sea-Derived Micromonospora rosaria SCSIO N160, Organic Letters, 2017,19(3):592–595

  4. Ruidong Chen+, Qingbo Zhang+, Bin Tan, Liujuan Zheng, Huixian Li, Yiguang Zhu, and Changsheng Zhang*,Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides,Organic Letters, 2017,19(20):5697-5700

  5. Liang Ma+, Wenjun Zhang, Yiguang Zhu, Guangtao Zhang, Haibo Zhang, Qingbo Zhang, Liping Zhang, Chengshan Yuan, Changsheng Zhang*, Identification and Characterization of a Biosynthetic Gene Cluster for Tryptophan Dimers in Deep Sea-Derived Streptomyces sp. SCSIO 03032, Applied Microbiology and Biotechnology, 2017,101(15):6123-36

  6. Xiaodong Jiang*, Qingbo zhang, Yiguagn Zhu, Fangling Nie, Zhengchao Wu, Chunfang Yang, Liping Zhang, Xinpeng Tian, ChangshengZhang*, Isolation, structure elucidation and biosynthesis of benzo[b]fluorene nenestatin A from deep-sea derived Micromonospora echinospora SCSIO 04089, Tetrahedron, 2017,73(26):3585–3590

 

2016

  1. Zhu Yiguang#, Picard MÈ#, Zhang Qingbo, Barma J, Després X, Mei Xiangui, Zhang Liping, Duvignaud J, Couture M, Zhu Weiming, Shi Rong*, Zhang Changsheng*. Flavoenzyme CrmK-Mediated Substrate Recycling in Caerulomycin BiosynthesisChemical Science, 2016, DOI: 10.1039/C6SC00771F.

  2. Zhu Yiguang#, Xu Jinxin#, Mei Xiangui#, Feng Zhan, Zhang Liping, Zhang Qingbo, Zhang Guangtao, Zhu Weiming*, Liu Jinsong*, Zhang Changsheng*. Biochemical and Structural Insights into the Aminotransferase CrmG in Caerulomycin BiosynthesisACS Chemical Biology, 2016,11(4):943-952.

  3. Zhang Guangtao, Zhang Wenjun, Saha Subhasish, Zhang Changsheng*. Recent Advances in Discovery, Biosynthesis and Genome Mining of MedicinallyRelevant Polycyclic Tetramate Macrolactams, Current Topics in MedicinalChemistry, 2016, DOI: 10.2174/156802661666615101211281.

  4. Zhang Haibo#, Saurav Kumar#, Yu Ziquan, Tibor Kurtan, Mándi Attila, Li Jie, Tian Xinpeng, Zhang Qingbo, Zhang Wenjun, Zhang Changsheng*. α-Pyrones with Diverse Hydroxy Substitutions from Three Marine-Derived Nocardiopsis Strains. Journal of Natural Products, 2016, 79(6): 1610-1618.

 

2015

  1. Huixian Li, Yu Sun(共同第一),Qingbo Zhang, Yiguang Zhu, Sumei Li, Ang Li, Changsheng Zhang*. Elucidating the cyclization cascades in xiamycin biosynthesis by substrate synthesis and enzyme characterizations. Organic Letters. 2015,17(2):306-9

  2.  Chunfang Yang ,Chunshuai Huang ,Wenjun Zhang *,Yiguang Zhu ,Changsheng Zhang *. Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer. Organic Letters. 2015,17(21):5324-5327

  3. Yiguang Zhu#,Wenjun Zhang#,Yaolong Chen, Chengshan Yuan, Haibo Zhang, Guangtao Zhang, Liang Ma, Qingbo Zhang, Xinpeng  Tian, Si Zhang, Changsheng Zhang*. Characterization of Heronamide Biosynthesis Reveals A Tailoring Hydroxylase and Indicates Migrated Double Bonds. ChemBioChem. 2015,16(14):2086-2093

 

2014 

  1. Zhang Guangtao, Zhang Wenjun, Zhang Qingbo, Shi Ting, Ma Liang, Zhu Yiguang, Li Sumei, Zhang Haibo, Zhao Yilei, Shi Rong, Zhang Changsheng*. Mechanistic Insights Into Polycycle Formation by Reductive Cyclization in Ikarugamycin Biosynthesis. Angew. Chem. Int. Ed., 2014, 2014,53:4840-4844  

  2. Peng Fu,Yiguang Zhu(共同第一),Xiangui Mei,Yi Wang,Haijian Jia,Changsheng Zhang*and Weiming Zhu*. Acyclic Congeners from Actinoalloteichus cyangriseus Provide Insights into Cyclic Bipyridine Glycoside Formation. Organic Letters. 2014,16(16),4264-4267  

  3. Yaolong Chen†,Wenjun Zhang†,Yiguang Zhu,* Qingbo Zhang, Xinpeng Tian, Si Zhang,and Changsheng Zhang*. Elucidating Hydroxylation and Methylation Steps Tailoring Piericidin A1 Biosynthesis. Organic Letters. 2014,16(3),736-739  

  4. Wenjun Zhang, Sumei Li, Yiguang Zhu, Yuchan Chen, Yaolong Chen, Haibo Zhang, Guangtao Zhang, Xinpeng Tian, Yu Pan, Si Zhang, Weimin Zhang, and Changsheng Zhang*. Heronamides D–F, Polyketide Macrolactams from the Deep-Sea-Derived Streptomyces sp. SCSIO 03032. Journal of Natural Products. 2014,77(2),388-391  

  5. Wenjun Zhang , Liang Ma(共同第一), Sumei Li, Zhong Liu, Yuchan Chen , Haibo Zhang, Guangtao Zhang, Qingbo Zhang, Xinpeng Tian , Chengshan Yuan , Si Zhang , Weimin Zhang , and Changsheng Zhang *† †.Indimicins A–E, Bisindole Alkaloids from the Deep-Sea-Derived Streptomyces sp. SCSIO 03032. Journal of Natural Products. 2014,77(8):1887-1892  

  6. Yaolong Chen†,Wenjun Zhang†,Yiguang Zhu,* Qingbo Zhang, Xinpeng Tian, Si Zhang,and Changsheng Zhang*. Elucidating Hydroxylation and Methylation Steps Tailoring Piericidin A1 Biosynthesis. Organic Letters. 2014,16(3),736-739  

  7. Wenjun Zhang, Sumei Li, Yiguang Zhu, Yuchan Chen, Yaolong Chen, Haibo Zhang, Guangtao Zhang, Xinpeng Tian, Yu Pan, Si Zhang, Weimin Zhang, and Changsheng Zhang*. Heronamides D–F, Polyketide Macrolactams from the Deep-Sea-Derived Streptomyces sp. SCSIO 03032. Journal of Natural Products. 2014,77(2),388-391      

  

2013 

  1. Ruidong Chen+, Haibo Zhang+, Gaiyun Zhang, Sumei Li, Guangtao Zhang, Yiguang Zhu, Jinsong Liu, Changsheng Zhang*. Characterizing Amosamine Biosynthesis in Amicetin Reveals AmiG as a Reversible Retaining Glycosyltransferase. Journal of the American Chemical Society 2013,135:12152-12155  

  2. Yiguang Zhu, Qingbo Zhang, Sumei Li, Qinheng Lin, Peng Fu, Guangtao Zhang, Haibo Zhang, Rong Shi, Weiming Zhu, Changsheng Zhang*. Insights into Caerulomycin A Biosynthesis:A Two-Component Monooxygenase CrmH-Catalyzed Oxime Formation. Journal of the American Chemical Society 2013,135 (50):18750-18753  

  3.Sumei Li, Ji Xiao, Yiguang Zhu, Guangtao Zhang, Chunfang Yang, Haibo Zhang, Liang Ma, Changsheng Zhang*. Dissecting Glycosylation Steps in Lobophorin Biosynthesis Implies an Iterative Glycosyltransferase. Organic Letters 2013,15(6):1374-1377  

  4.Zhengchao Wu, Sumei Li, Jie Li, Yuchan Chen, Kumar Saurav, Qingbo Zhang, Haibo Zhang, Wenjun Zhang, Weimin Zhang, Si Zhang, Changsheng Zhang*. Antibacterial and Cytotoxic New Napyradiomycins from the Marine-Derived Streptomyces sp. SCSIO 10428. Marine Drugs 2013,11:2113-2125  

  5.Ji Xiao, Qingbo Zhang, Yiguang Zhu, Sumei Li, Guangtao Zhang, Haibo Zhang, Kumar Saurav, Changsheng Zhang*. Characterization of the sugar-O-methyltransferase LobS1 in lobophorin biosynthesis. Applied Microbiology and Biotechnology 2013,97(20):9043-9053  

  6.Zhengchao Wu, Sumei Li, Sangjip Nam, Zhong Liu, Changsheng Zhang*. Nocardiamides A and B, Two Cyclohexapeptides from the Marine-Derived Actinomycete Nocardiopsis sp. CNX037. Journal of Natural Products 2013,76:694-701  

  7.Qingbo Zhang, Sumei Li, Yuchan Chen, Xinpeng Tian, Haibo Zhang, Guangtao Zhang, Yiguang Zhu,Si Zhang, Weimin Zhang, Changsheng Zhang*. New diketopiperazine derivatives from a deep-sea-derived Nocardiopsis alba SCSIO 03039. Journal of Antibiotics 2013,66:31-36  

  

2012 

  1.Yiguang Zhu, Peng Fu, Qinheng Lin, Guangtao Zhang, Haibo Zhang, Sumei Li, Jianhua Ju, Weiming Zhu, Changsheng Zhang*. Identification of caerulomycin A gene cluster implicates a tailoring amidohydrolase. Organic Letters. 2012, 14(11):2666-2669  

  2.Wenjun Zhang, Zhong Liu, Sumei Li, Tingting Yang, Qingbo Zhang, Liang Ma, Xinpeng Tian, Haibo Zhang, Caiguo Huang, Si Zhang, Jianhua Ju, Yuemao Shen , and Changsheng Zhang*. Spiroindimicins A-D: new bisindole alkaloids from a deep-sea-derived actinomycete. Organic Letters. 2012, 14 (13):3364-3367  

  3.Qingbo Zhang, Huixian Li, Sumei Li, Yiguang Zhu, Guangtao Zhang, Haibo Zhang, Wenjun Zhang, Rong Shi, and Changsheng Zhang*. Carboxyl Formation from Methyl via Triple Hydroxylations by XiaM in Xiamycin A Biosynthesis. Organic Letters. 2012, 14 (24): 6142–6145  

  4.Huixian Li, Qingbo Zhang, Sumei Li, Yiguang Zhu, Guangtao Zhang, Haibo Zhang, Xinpeng Tian, Si Zhang, Jianhua Ju, Changsheng Zhang*. Identification and characterization of xiamycin A and oxiamycin gene cluster reveals an oxidative cyclization strategy tailoring indolosesquiterpene biosynthesis. Journal of the American Chemical Society. 2012, 134(21): 8996-9005  

  5.Gaiyun Zhang, Haibo Zhang, Sumei Li, Ji Xiao, Yiguang Zhu, Siwen Niu, Jianhua Ju, Changsheng Zhang*. Characterization of the amicetin biosynthesis gene cluster from Streptomyces vinaceusdrappus NRRL 2363 implicates two alternative strategies for amide bond formation. Applied and Environmental Microbiology. 2012, 78(7):2393-2401  

  6.Qingbo Zhang, Attila Mandi, Sumei Li, Yuchan Chen, Wenjun Zhang, Xinpeng Tian, Haibo Zhang, Huixian Li, Weimin Zhang, Si Zhang, Jianhua Ju, Tibor Kurtan, Changsheng Zhang*. N-N-Coupled Indolo-sesquiterpene Atropo-Diastereomers from a Marine-Derived Actinomycete. European Journal of Organic Chemistry. 2012, 27, 5256-5262  

  7.Wenjun Zhang, Zhong Liu, Sumei Li, Yongzhi Lu, Yuchan Chen,Haibo Zhang, Guangtao Zhang, Yiguang Zhu,Gaiyun Zhang, Weimin Zhang,Jinsong Liu, and Changsheng Zhang*, Fluostatins IK from the South China Sea-Derived Micromonospora rosaria SCSIO N160. J. Nat. Prod. 2012, 75, 19371943  

  

2011 

  1.Xiao Y†, Li S†, Niu S, Ma L, Zhang G, Zhang H, Zhang GY, Ju J, Zhang C*. Characterization of Tiacumicin B Biosynthetic Gene Cluster Affording Diversified Tiacumicin Analogues and Revealing a Tailoring Dihalogenase. Journal of the American Chemical Society.  2011, 133 (4): 1092–1105.  

  2.Niu S†, Hu T†, Li S, Xiao Y, Ma L, Zhang G. Zhang H, Zhang S, Yang X, Zhang C*. Characterization of a Sugar-O-methyltransferase TiaS5 Affords New Tiacumicin Analogues with Improved Antibacterial Property and Reveals Substrate Promiscuity. ChemBioChem, 2011, 12(11): 1740-1748.  

  3.Li S, Tian XP, Niu S, Zhang W, Chen Y, Zhang H, Zhang W, Li WJ, Zhang S, Ju J, Zhang C*. Pseudonocardians A-C, New Diazaanthraquinone Derivatives from a Deep-Sea Actinomycete Pseudonocardia sp. SCSIO 01299. Mar. Drugs, 2011, 2011, 9(8): 1428-1439..   

  4.Niu S, Li S, Chen Y, Tian X, Zhang H, Zhang G, Zhang W, Yang X, Zhang S, Ju J, Zhang C*. Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127. J. Antibiot., 2011, 64(11):711-716.   

  5.Gong L, Xiao Y, Liu Q, Li S, Zhang C*, Liu J*. Preliminary X-ray crystallographic analysis of the glycosyltransferase from a marine Streptomyces species. Acta Crystallogr Sect F Struct Biol Cryst Commun., 2011, 67(1): 136-139.  

  6.Williams GJ, Yang J, Zhang C, Thorson JS*. Recombinant E. coli Prototype Strains for in Vivo Glycorandomization. ACS Chem. Biol., 2011, 6(1): 94-100.   

  7.Li J, Zhang GT, Yang J, Tian XP, Wang FZ, Zhang C, Zhang S, Li WJ*. Marina mesophila gen. nov., sp. nov., a novel thermoactinomycete isolated from a deep sea sediment, and emended description of the family Thermoactinomycetaceae Matsuo et al. 2006 emend. Yassin et al. 2009, emend. Von Jan et al. 2010. Int. J. Syst. Evol. Microbiol., 2011, doi:10.1099/ijs.0.035071-0.  

  8.Tian XP, Long LJ, Wang FZ, Xu Y, Li J, Zhang J, Zhang C, Zhang S*, Li WJ*. Streptomyces nanhaiensis sp. nov., a novel marine streptomycete isolated from a deep sea sediment in Southern China Sea. Int. J. Syst. Evol. Microbiol., 2011, doi: 10.1099/ijs.0.031591-0.  

 

2008 

  1.Zhang C, Jiang J, Morreti R, Thorson JS*. The In Vitro Characterization of Polyene Glycosyltransferases AmphDI and NysDI. ChemBioChem, 2008, 9(15): 2506-2514.   

  2.Zhang C, Bitto E, Goff RD, Griffith BR, Albermann C, Bingman CA, Phillips Jr GN*, Thorson JS*. Biochemical and Structural Insights of the Early Glycosylation Steps in Calicheamicin Biosynthesis. Chem. Biol., 2008, 15(8): 842-853.  

  3.Williams GJ, Goff RD, Zhang C, Thorson JS*. Optimizing glycosyltransferase specificity via ‘hot spot’ saturation mutagenesis presents a new catalyst for novobiocin glycorandomization. Chem. Biol., 2008, 15(4): 393-401.  

  4.Singh S, McCoy JG, Zhang C, Bingman CA, Phillips Jr GN*, Thorson JS*. Structure and Mechanism of the Rebeccamycin Sugar 4-O-Methyltransferase RebM. J. Biol. Chem., 2008, 283(33): 22628-22636.   

 

2007 

  1.Zhang C, Fu Q, Albermann C, Li L, Thorson JS*. The In Vitro Characterization of the Erythronolide Mycarosyltransferase EryBV and Its Utility in Macrolide Diversification. ChemBioChem, 2007, 8(4): 385-390.  

  2.Zhang C, Albermann C, Fu X, Thorson JS*. The In Vitro Characterization of the Iterative Avermectin Glycosyltransferase AveBI Reveals Reaction Reversibility and Sugar Nucleotide Flexibility.Journal of the American Chemical Society., 2006, 128(51): 16420-16421.   

 

2006 

  1.Zhang C, Griffith BR, Fu Q, Albermann C, Fu X, Lee IK, Li L, Thorson JS*. Exploiting the Reversibility of Natural Product Glycosyltransferase-catalyzed Reactions. Science, 2006, 313(5791): 1291-1294.   

  2.Zhang C, Albermann C, Fu X, Peters NR, Chisholm JD, Zhang G, Gilbert EJ, Wang PG, Van Vranken DL, Thorson JS*. RebG- and RebM-catalyzed Indolocarbazole Diversification. ChemBioChem, 2006, 7(5): 795-804.   

  3.Zhang C, Weller RL, Thorson JS, Rajski SR*. Natural Product Diversification Using Non-natural Cofactor Analogues of S-adenosyl-L-methionine. Journal of the American Chemical Society., 2006, 128(9): 2760-2761. 

  4.Borisova SA, Zhang C, Takahashi H, Zhang H, Wong AW, Thorson JS, Liu H-w*. Substrate Specificity of the Macrolide-Glycosylating Enzyme Pair DesVII/DesVIII: Opportunities, Limitations and Mechanistic Hypotheses. Angew. Chem. Intl. Ed., 2006, 45(17): 2748-2753.   

  5.Gao Q, Zhang C, Blanchard S, Thorson JS*. Deciphering indolocarbazole and enediyne aminopentose biosynthesis through comparative genomics: New insights and tools from the Actinomadura melliaura AT2433 biosynthetic locus. Chem. Biol., 2006, 13(7):733-743.  

  6.Singh S, Hager MH, Zhang C, Griffith BR, Lee MS, Hallenga K, Markley JL and Thorson JS*. Structural insight into self-sacrifice mechanism of enediyne resistance. ACS Chem. Biol., 2006, 1(7): 451-460.   

 

2005 

  1.Fu X, Albermann C, Zhang C, Thorson JS*. Diversifying Vancomycin via Chemoenzymatic Strategies. Org. Lett., 2005, 7(8): 1513-1515.

 

2003 

  1.Zhang C, Podeschwa M, Block O, Altenbach HJ, Piepersberg W, Wehmeier UF*. Identification of a 1-epi-valienol 7-kinase activity in the producer of acarbose, Actinoplanes sp. SE50/110. FEBS Lett., 2003, 540(1-3): 53-57.  

  2.Zhang C, Podeschwa M, Altenbach HJ, Piepersberg W and Wehmeier UF*. The acarbose-biosynthetic enzyme AcbO from Actinoplanes sp. SE 50/110 is a 2-epi-5-epi-valiolone-7-phosphate 2-epimerase. FEBS Lett., 2003, 540(1-3): 47-52.   

  3.Fu X, Albermann C, Jiang J, Liao J, Zhang C, Thorson JS*. Antibiotic optimization via in vitro glycorandomization. Nat. Biotechnol., 2003, 21(12): 1467-1469.   

  

2002 

  1.Zhang C, Stratmann A, Block O, Brückner R, Podeschwa M, Altenbach HJ, Wehmeier UF and Piepersberg W*. Biosynthesis of the C7-cyclitol Moiety of Acarbose in Actinoplanes Species SE50/110. 7-O-phosphorylation of the initial cyclitol precursor leads to proposal of a new biosynthetic pathway. J. Biol. Chem., 2002, 277(25): 22853-22862.   

 

授权专利:

  1. 厦霉素A和氧厦霉素的生物合成基因簇及其应用,ZL201210146664.x,张长生,李慧贤,张庆波,李苏梅,朱义广,张光涛,张海波,田新朋,张偲,鞠建华

  2. 友菌素的生物合成基因簇及其应用,ZL201210030835.2,张长生,张海波,李苏梅,张改云,张光涛,朱义广,陈瑞东,肖吉,鞠建华

  3. 链霉菌和吲哚倍半萜类化合物及其制备方法和在制备抗菌抗肿瘤药物中的应用,ZL201210146953.x,张长生,张庆波,李苏梅,田新朋,张文军,张海波,李惠贤,张偲,鞠建华

  4. 一种小单孢菌及利用该菌制备多种抗生素的方法,ZL201210467946.X,张长生,张文军,李苏梅,张海波,张改云,张光涛,朱义广

  5. 一种链霉菌及利用该菌发酵制备抗霉素类抗生素的工艺,ZL201010520348.5,张长生,李苏梅,田新朋,牛四文,张文军,鞠建华,张偲

  6. 一种链霉菌及利用该菌制备多种抗生素的工艺,ZL201010603179.1,张长生,李苏梅,田新朋,牛四文,鞠建华,张偲

  7. 四种台勾霉素类化合物及其制备方法和在制备抗菌药物中的应用,ZL201010526416.9,张长生,李苏梅,肖毅,牛四文,鞠建华

  8. 抗生素Pseudonocardian AB及其制备方法和在制备抗菌、抗肿瘤药物中的应用,ZL201110231993.X,张长生,李苏梅,田新朋,张文军,张海波,张光涛,张偲,鞠建华

  9. 抗生素Lobophorin EF及其制备方法和在制备抗菌、抗肿瘤药物中的应用,ZL201110149558.2,张长生,李苏梅,牛四文,田新朋,张光涛,张海波,张偲,鞠建华

  10. 六种台勾霉素类化合物及其制备方法和在制备抗菌药物中的应用,ZL201110104051.5,张长生,牛四文,胡涛,李苏梅,肖毅,马亮,张光涛,张海波,鞠建华

  11. 一种假诺卡氏菌及利用其制备Deoxynyboquinone的方法,ZL201110231994.4,张偲,张长生,田新朋,李苏梅,张文军,张海波,张光涛,尹浩,鞠建华

  12. 链霉菌、抗肿瘤化合物Spiroindimycin A-D及其制备方法和应用, ZL201210087537.7,张长生,张文军,田新朋,李苏梅,张庆波,马亮,张海波,张偲,鞠建华

  13. 台勾霉素的生物合成基因簇及其应用,ZL201010592416.9,张长生,肖毅,李苏梅,牛四文,张光涛,张海波,胡涛,鞠建华

  14. 链霉菌、抗肿瘤化合物Spiroindimycin A-D及其制备方法和应用,特许第5826406PCT国际专利(日本),张长生,张文军,田新朋,李苏梅,张庆波,马亮,张海波,张偲,鞠建华 

  15. 链霉菌、新化合物及其制备方法和在制备抗菌抗肿瘤药物中的应用, ZL201310180810.5, 张长生,吴正超,李苏梅,李洁,库马.萨乌拉夫,张庆波,张海波,张文军,张偲

  16. 一种斑鸠霉素的生物合成基因簇及其应用, ZL201410120626.6, 张长生,张光涛,张文军,张庆波,朱义广,张海波,李苏梅,马亮

  17. 抗生素Indimicins AE及其制备方法和在制备抗肿瘤药物中的应用, ZL201410214540.X,张长生,张文军,马亮,李苏梅,张庆波,张海波,张光涛

  18. 抗生素difluostatin A及其制备方法和在制备抗菌药物中的应用,ZL201510650332.9,张长生,张文军,杨春芳,黄春帅,朱义广

  19. 新化合物及其制备方法和在制备抗菌抗肿瘤药物中的应用, ZL201510512966.8,张长生,吴正超,李苏梅,李洁,库马.萨乌拉夫,张庆波,张海波,张文军,张偲

 

学科组建设

责任研究员:张长生

副研究员:张海波,朱义广,张文军,张光涛,张庆波

助理研究员:张丽萍,杨春芳

博士后:余子全,袁呈山,Jannu Vinay Gopal ,刘智文

博士研究生:黄春帅,金红波(直博生),刘威(中山大学联合培养),谭彬,Bidhan Chandra De (CAS-TWAS President’s Fellowship),蒋晓东Imran Khan
硕士研究生:黄艳冰,方壮杰,方春艳
行政助理:于艳玲

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