周祥山
发布人:生工学院网站管理员  发布时间:2016-10-19   动态浏览次数:18

 

祥山

生物化工专业:博士生导师/硕士生导师
        生物工程专业:博士生导师/硕士生导师

生物工程领域:工程硕士生导师

    

  

     男,博士,华东理工大学生物工程学院,生物反应器工程国家重点实验室教授,博士生导师。
    1974
9月生,2002年获华东理工大学生物化工博士学位,2001年留校华东理工大学生物工程学院,生物反应器工程国家重点实验室工作。2004年升副教授,2008年德国卡尔斯鲁尔大学访问学者,2009年升教授,博士生导师。中国微生物学会海洋微生物学专业委员会副主任委员。中国生物化学与分子生物学会海洋生物化学与分子生物学分会第3届理事会常务理事。上海市药学会第十届理事会海洋药物专业委员会委员。

获奖
2002
年获上海市高校“三枪杯”创造发明奖,2002年获罗门哈斯奖学金,20039月获得华东理工大学优秀博士论文奖,2005年获华东理工大学青年学术骨干教师,2005年获得上海市优秀青年教师后备人选资助,2008年获上海高校优秀青年教师称号,2009年获上海市青年科技启明星。2007年获国家海洋局海洋创新成果奖一等奖(排名第七),2010年获山东省科技进步一等奖(排名第六),2011年获山东省科技进步一等奖(排名第一)。2013年入选国家“万人计划”首批“中青年科技创新领军人才”。已在国内外发表论文50余篇,其中以第一作者或通讯作者发表SCI论文26篇。申请中国发明专利20余项,其中12项已授权。
目前主要研究方向为微生物制药,真核微生物生物技术,用酵母和霉菌产药用蛋白或药用化合物。

主要研究方向
1
毕赤酵母表达药用蛋白,及表达系统优化及拓展。开发甲醇传感器,通过对发酵条件优化及基因改造提高重组药用蛋白产量,并减少目标蛋白降解以提高产品质量。毕赤酵母表达的水蛭素的产量已超过4.5 g/L,而此前文献报道的最高产量为1.5 g/L。为了减小毒性蛋白对宿主细胞的影响,在毕赤酵母细胞器过氧化物酶体中表达重组蛋白酪氨酸激酶。通过对毕赤酵母AOX1启动子分子调控机理进行研究,开发了增强型 AOX1改良启动子。为了便于高密度可控诱导表达,同时避免甲醇在工业化上的防暴、GMP规范等问题,通过基因改造首次开发了非甲醇诱导型AOX1启动子新型表达系统。

2 丝状真菌(霉菌)发酵产活性药用化合物与分子基因改造。通过对菌丝形态、前体代谢调控、生物合成途径、发酵工程操作条件及反应器结构优化与控制,提高霉菌产药用活性次级代谢产物的产量。将抗肿瘤化合物灰绿霉素A产量由4 mg/L提高到150 mg/L,放大到500升。抗肿瘤化合物1403C产量由1.3 mg/L提高到1.5 g/L,提高超过1100倍。运用分子生物学手段对霉菌进行基因改造,提高与优化次级代谢。

3 中药分子鉴定。应用基因组、蛋白组技术对中药,特别是阿胶、龟甲胶、鹿角胶等胶类进行分子鉴定。
承担科研课题
主持国家自然科学基金、国家十二五863项目、“十二五”“重大新药创制”科技重大专项。
硕士招生专业:生物化工,微生物与生化药学,生物工程(工程硕士)
博士招生专业:生物化工


近期发表的部分论文(*为通讯作者):
1. Limei Gao, Menghao Cai* , Wei Shen, Siwei Xiao, Xiangshan Zhou and Yuanxing Zhang. Engineered fungal polyketide biosynthesis in Pichia pastoris: a potential excellent host for polyketide production. Microbial Cell Factories 2013, 12:77
2. Weiqiang Zhou, Menghao Cai*, Jiushun Zhou, Tao Jiang, Jiao Zhou, Meixia Wang, Xiangshan Zhou*, Yuanxing Zhang. Nutrition and bioprocess development for ef?cient biosynthesis of an antitumor compound from marine-derived fungus. Journal of Industrial Microbiology & Biotechnology. 2013, 40:1131-1142.
3. Jiushun Zhou, Menghao Cai*, Tao Jiang, Weiqiang Zhou, Wei Shen, Xiangshan Zhou, Yuanxing Zhang. Mixed carbon source control strategy for enhancing alginate lyase production by marine Vibrio sp. QY102. Bioprocess and Biosystem Engineering. 2013. DOI 10.1007/s00449-013-1024-1.
4. Haifeng Liu, Xiangshan Zhou*, Fusheng Xie, Jinhua You, Yuanxing Zhang*. An efficient trypsin digestion strategy for improving desB30 productivity from recombinant human insulin precursor fusion protein. Process Biochemistry, 2013,48 (5-6): 965–971.
5. Haifeng Liu, Xiangshan Zhou*, Fusheng Xie, Jinhua You, Yuanxing Zhang*. An efficient trypsin digestion strategy for improving desB30 productivity from recombinant human insulin precursor fusion protein. Process Biochemistry, 2013,48 (5-6): 965–971
6. Menghao Cai, Zhe Fang, Chuanpeng Niu, Xiangshan Zhou*, Yuanxing Zhang. Light regulation on growth, development and secondary metabolism of marine-derived filamentous fungi. Folia Microbiologica. 2013 (Accept)
7. Menghao Cai, Xueqian Sun, Xiangshan Zhou*, Yuanxing Zhang*. Roles of cobalt in biosynthesis stimulation of a cytotoxic compound from marine-derived Aspergillus glaucus. Process Biochemistry. 2012, 12 (47): 2267–2274
8. Chuanpeng Niu, Menghao Cai, Yuanxing Zhang, Xiangshan Zhou*. Biosynthetic origin of the carbon skeleton of a novel  anti-tumor compound, haloroquinone, from a marine-derived fungus, Halorosellinia sp. Biotechnology Letters, 2012, 34: 2119-2124
9. Zhe Fang, Ying Zhang, Menghao Cai, Jian Zhang, Yuanxing Zhang, Xiangshan Zhou*. Improved gene targeting frequency in marine-derived filamentous fungus Aspergillus glaucus by disrupting ligD. Journal of Applied Genetics. 2012, 53(3): 355?362
10. Menghao Cai, Xiangshan Zhou*, Jian Lu, Weimin Fan, Jiushun Zhou, Chuanpeng Niu, Li Kang, Xueqian Sun, Yuanxing Zhang*. An integrated control strategy for the fermentation of the marine-derived fungus Aspergillus glaucus for the production of Anti-cancer polyketide. Marine Biotechnology. 2012, 14: 665-671.
11. Chao Yu, Menghao Cai, Li Kang, Yuanxing Zhang , Xiangshan Zhou*. Significance of seed culture methods on mycelial morphology and production of a novel anti-cancer anthraquinone by marine mangrove endophytic fungus Halorosellinia sp. (No. 1403). Process Biochemistry. 2012, 47: 422-427
12. Li Kang, Menghao Cai, Chao Yu, Yuanxing Zhang, Xiangshan Zhou*. Improved production of the anticancer compound 1403C by glucose pulse feeding of marine Halorosellinia sp. (No.1403) in submerged culture. Bioresource Technology, 2011, 102: 10750-10753
13. Pin Lv, Yingjie Zhao, Fei Qi, Xiangshan Zhou*, Jinhua You, Yufeng Qin, Yuanxing Zhang. Authentication of equine DNA from highly processed donkey-hide glue (colla corii asini) using SINE element. Journal of Food and Drug Analysis, 2011, 19: 120-130.
14. Menghao Cai, Xiangshan Zhou*, Jian Lu, Weimin Fan, Chuanpeng Niu, Jiushun Zhou, Xueqian Sun, Li Kang, Yuanxing Zhang*. Enhancing aspergiolide A production from a shear-sensitive and easy-foaming marine-derived filamentous fungus Aspergillus glaucus by oxygen carrier addition and impeller combination in a bioreactor. Bioresource Technology, 2011, 102: 3584-3586.
15. Ping Zhang, Wenwen Zhang, Xiangshan Zhou*, Peng Bai, James M. Cregg, Yuanxing Zhang*. Catabolite repression of Aox in Pichia pastoris is dependent on hexose transporter PpHxt1 and Pexophagy. Applied and Environmental Microbiology, 2010, 76(18): 6108-6118
16. Menghao Cai, Xiangshan Zhou*, Jiushun Zhou, Chuanpeng Niu, Xueqian Sun, Yuanxing Zhang*. Efficient strategy for enhancing aspergiolide A production by citrate feedings and its effects on sexual development and growth of marine-derived fungus Aspergillus glaucus. Bioresource Technology, 2010, 101: 6059-6068.
17. Xueqian Sun, Xiangshan Zhou*, Menghao Cai, Jiushun Zhou, Yuanxing Zhang*. Significant stimulation of o-phthalic acid in biosynthesis of aspergiolide A by a marine-derived fungus Aspergillus glaucus. Bioresource Technology, 2010, 101: 3609-3616.
18. Pin Lv, Xiangshan Zhou*, Jinhua You, Yufeng Qin, Bang-Ce Ye, Yuanxing Zhang. Tortoise DNA detection from highly processed tortoise shell using SINE element. Journal of Food and Drug Analysis, 2010, 18(2): 113-119.
19. Yaoji Xuan, Xiangshan Zhou*, Wenwen Zhang, Xiao Zhang, Zhiwei Song, Yuanxing Zhang. An upstream activation sequence control the expression of AOX1 gene in Pichia pastoris. FEMS Yeast Research, 2009, 9: 1271-1282
20. Lin Chen, Chao Yu, Xiangshan Zhou*, Yuanxing Zhang. Rational introduction of disulfide bond to enhance optimal temperature of Lipomyces starkeyi α-dextranase expressed in Pichia pastoris. Journal of Microbiology and Biotechnology, 2009, 19(12): 1506-1513
21. Ya Wang, Yaoji Xuan, Ping Zhang, Xi Jiang, Zhenhua Ni, Linjiang Tong, Xiangshan Zhou*, Liping Lin, Jian Ding, Yuanxing Zhang. Targeting expression of the catalytic domain of kinase insert domain receptor (KDR) in the peroxisomes of Pichia pastoris. FEMS Yeast Research, 2009, 9: 732-741
22. Pin Lv, Xiangshan Zhou*, Jinhua You, Bang-Ce Ye, and Yuanxing Zhang. Extraction of trace amount of severely degraded DNA. Zeitschrift für Naturforschung C (Z. Naturforsch. C), 2009, 64c: 581-589
23. Xueqian Sun, Xiangshan Zhou*, Menghao Cai, Kejing Tao, Yuanxing Zhang*. Identified biosynthetic pathway of aspergiolide A and a novel strategy to increase its production in a marine-derived fungus Aspergillus glaucus by feeding of biosynthetic precursors and inhibitors simultaneously. Bioresource Technology, 2009, 100(18): 4244-4251
24. Kejing Tao, Lin Du, Xueqian Sun, Menghao Cai, Tianjiao Zhu, Xiangshan Zhou*, Qianqun Gu, Yuanxing Zhang. Biosynthesis of aspergiolide A, a novel antitumor compound by a marine-derived fungus Aspergillus glaucus via the polyketide pathway. Tetrahedron Letters, 2009, 50 (9): 1082–1085
25. Meng-Hao Cai, Xue-Qian Sun, Ke-Jing Tao, Xiang-Shan Zhou*, Yuan-Xing Zhang*. Statistical optimization of medium composition for aspergiolide A production by marine-derived fungus Aspergillus glaucus. Journal Industrial Microbiology & Biotechnology, 2009, 36(3): 381-389
26. Zhenhua Ni, Xiangshan Zhou*, Xueqian Sun, Ya Wang, Yuanxing Zhang. Decrease of hirudin degradation by deleting the KEX1 gene in recombinant Pichia pastoris. Yeast, 2008, 25: 1-8
27. Lin Chen, Xiangshan Zhou*, Weimin Fan and Yuanxing Zhang. Expression, purification and characterization of a recombinant Lipomyces starkey dextranase in Pichia pastoris. Protein Expression and Purification, 2008, 58: 87-93
28. Chun Wei, Xiangshan Zhou, Yuanxing Zhang*. Improving intracellular production of recombinant protein in Pichia pastoris using an optimized preinduction glycerol-feeding scheme. Applied Microbiology and Biotechnology, 2008, 78: 257-264
29. 
赵英杰,吕品,周祥山*,赵英杰. 家驴基因组高度重复DNA序列的分离及其文库的构建. 华中农业大学学报, 2011, 30: 563-567
30. 
张盈,沈伟,蔡孟浩,周祥山*,张元兴. 海洋真菌灰绿曲霉地标蛋白编码基因AgTeaA的克隆与序列分析. 生物技术通报, 2011, 12: 157-161,174.
31. 
康丽,蔡孟浩,范卫民,陆健,周祥山*,张元兴. 海洋红树林内生真菌产抗肿瘤活性化合物1403C发酵条件的优化. 生物技术通报, 2011, 12: 199-204
32. 
余超,周祥山*,康丽,邹武,张元兴. 代谢途径抑制剂及前体对海洋红树林内生真菌No.1403产抗肿瘤化合物1403C的影响. 生物技术通报, 2010, 11: 199-205
33. 
张平,周祥山*,张元兴. 毕赤酵母碳源阻遏因子编码基因PpMIG1PpMIG2的克隆与序列分析. 生物技术通报, 2010, 11: 221-229
34. 
方喆,周祥山*,张健,张盈,张元兴. 海洋真菌灰绿曲霉蓝光感应基因Agwc1的克隆、鉴定与序列分析. 生物技术通报, 2010, 11: 191-198
35. 
张健,方喆,周祥山*,张元兴. 一个紫红曲霉HR-PKS基因MpER1的克隆及序列分析. 信阳师范学院学报(自然科学版), 2010, 23(3)395-401
36. 
宣姚吉,周祥山*,张元兴. 实时荧光定量PCR检测毕赤酵母基因组中外源基因拷贝数. 中国生物制品学杂志. 2009, 22(12): 1236-1239, 1243.
37. 
张文文,张平,宣姚吉,周祥山*,张元兴. 毕赤酵母己糖运载体HXT1基因缺失菌株的构建. 微生物学通报. 2009, 36(9): 1340-1344
38. 
茆建胜,周祥山*,张元兴. PDGFRβ受体型酪氨酸激酶的表达与纯化. 微生物学通报. 2009, 36(10): 1-6
39. 
魏春,周祥山*,张元兴. 比生长速率和氮源对毕赤酵母生产重组鲈鱼生长激素的影响. 微生物学通报. 2008, 35(10): 1522-1526.
40. 
江希,周祥山*,张元兴. ErbB2受体酪氨酸激酶激酶区的表达与纯化. 微生物学通报. 2008, 35(9): 1393-1397.
41. 
倪振华,周祥山*,张元兴. 毕赤酵母重组菌株直接基因缺失方法的研究. 微生物学通报2007, 34(6): 1198-1201
42. 
季青,周祥山,张元兴*. 鲑鱼降钙素前体多肽在毕赤酵母中的分泌表达. 中国医药工业杂志2007, 38(6):411-415
43. Anfeng Xiao, Xiangshan Zhou, Li Zhou, Yuanxing Zhang*. Improvement of cell viability and hirudin production by ascorbic acid in Pichia pastoris fermentation. Applied Microbiology and Biotechnology, 2006, 72(4): 837-844
44. Haifeng Liu, Xiangshan Zhou and Yuanxing Zhang*. Comparative investigation on different refolding strategies of recombinant human tissue-type plasminogen activator derivative. Biotechnology Letters, 2006, 28(7): 457-463
45. 
肖安风,周祥山,周利,张元兴* (2006) 应用流式细胞术检测毕赤酵母的细胞活性. 微生物学通报33(6):22?26.
46. 
肖安风,周祥山,周利,张元兴* (2006) 流式细胞术检测毕赤酵母发酵过程中胞内活性氧水平. 生物工程学报22(2):273?277.
47. 
张凌,周祥山,邵明非,张元兴 两阶段法发酵法培养重组酿酒酵母生产乙肝表面抗原. 华东理工大学学报,2005311):68-71 (EI: 2005149026103)
48. 
刘海峰,周祥山,庞甲佩,解锡军,张元兴. r-PAIL-11两种融合蛋白的柱上酶切. 中国医药工业杂志,200536(3)144-147
49. Jizhong Yang, Xiangshan Zhou, Yuanxing Zhang*. Improvement of recombinant hirudin production by controlling NH4+ concentration in Pichia pastoris fermentation. Biotechnology Letters, 2004, 26(12): 1013-1017
50. 
杨继忠,周祥山,尤金花,解锡军,解福生,张元兴*. 毕赤酵母发酵生产中的水蛭素降解顺序. 微生物通报,2004315):24-27
51. 
周祥山,范卫民,张元兴 甲醇抑制时重组毕赤酵母发酵的特性研究。生物工程学报 200319(5):618?622
52. 
周祥山,周卫斌,范卫民,张元兴,董美玉 重组毕赤酵母高密度发酵表达水蛭素过程中的产物生成和降解。中国生物制品学杂志 200316(1):24?27.
53. Xiang-Shan Zhou, Jian Lu, Wei-Min Fan, Yuan-Xing Zhang. Development of a responsive methanol sensor and its application in Pichia pastoris fermentation. Biotechnology Letters, 2002, 24(8): 643-646
54. Xiang-Shan Zhou, Yuan-Xing Zhang. Decrease of proteolytic degradation of recombinant hirudin produced by Pichia pastoris by controlling the specific growth rate. Biotechnology Letters 2002, 24(17): 1449?1453.
55. 
周祥山,范卫民,张元兴. 不同甲醇流加策略对重组毕赤酵母高密度发酵生产水蛭素的影响. 生物工程学报,200218(3)348-351
56. 
周卫斌,周祥山,张元兴. 毕赤酵母发酵液的脱色和重组水蛭素的分离. 生物工程学报, 2001, 17(6): 683~687

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E-mail:xszhou@ecust.edu.cn