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:1375

 

周祥山

生物化工专业:博士生/硕士生导师

生物工程专业:博士生/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;东阿阿胶股份有限公司副总裁、国家胶类中药工程技术研究中心主任。

1974年9月生,2002年获华东理工大学生物化工博士学位,2014年获中欧国际工商学院工商管理硕士学位(EMBA)。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。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,2013年获国家科技部“中青年科技创新领军人才”,2013年获国家“万人计划”中“科技创新领军人才”。2014年获山东省突出贡献中青年专家,2015年山东省泰山产业领军人才。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),2015年获山东省科技进步二等奖(排名第二)。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30篇。50多项发明专利(含2项PCT国际专利)已授权。

主要研究方向:

1.生物制药,含药用蛋白表达及真核生物表达系统改造;真菌分子改造与小分子药物发酵。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. 中药研发与分子鉴定。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。成功将多项生物技术应用于传统中药的现代化中。

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。


Publications:

1.Yuan Wu, Yanna Ren, Xiangshan Zhou, Menghao Cai*, Yuanxing Zhang*. Transcription factor Agseb1 affects development, osmotic stress response, and secondary metabolism in marine-derived Aspergillus glaucus.DOI: 10.1002/jobm.201700123.

2.Jinjia Wang, Xiaolong Wang, Lei Shi, Fei Qi, Ping Zhang, Yuanxing Zhang, Xiangshan Zhou*, Zhiwei Song*, Menghao Cai*. Methanol-independent protein expression by AOX1 promoter with trans-acting elements engineering and glucose-glycerol-shift induction in Pichia pastoris. Scientific Reports 2017, 7: 41850.

3.Yanyun Gao, Mengmeng Huang, Xiaoyue Sun, Xiaoxu Zhang, Yuanxing Zhang, Xiangshan Zhou*, Menghao Cai*. Single-site mutation of C363G or N463T strengthens thermostability improvement of IG181-182 deleted acidic α-amylase from deep-sea thermophile Geobacillus sp. Food Biotechnology. 2017, 2017, 31(1): 57-71.

4.Ying Xue, Chuixing Kong, Wei Shen, Chenxiao Bai, Yanna Ren, Xiangshan Zhou, Yuanxing Zhang, Menghao Cai*. Methylotrophic yeast Pichia pastoris as a chassis organism for polyketide synthesis via the full citrinin biosynthetic pathway. Journal of Biotechnology. 2017, 242:64-72

5.Shaomei Liu, Jiaxin Li, Yuan Wu, Yanna Ren, Qi Liu, Qiyao Wang, Xiangshan Zhou, Menghao Cai*, Yuanxing Zhang. De novo transcriptome sequencing of marine-derived Aspergillus glaucus and comparative analysis of metabolic and developmental variations in response to salt stress. Genes & Genomics. 2017, 39:317-329.

6.Mengmeng Huang, Yanyun Gao, Xiangshan Zhou, Yuanxing Zhang, Menghao Cai*. Regulating unfolded protein response activator HAC1p for production of thermostable raw-starch hydrolyzing α-amylase in Pichia pastoris. Bioprocess and Biosystem Engineering. 2017, 40:341-350

7.Siwei Xiao, Yanyun Gao, Xiaolong Wang, Wei Shen, Jinjia Wang, Xiangshan Zhou, Menghao Cai*, Yuanxing Zhang. Peroxisome-targeted and tandem repeat multimer expressions of human antimicrobial peptide LL37 in Pichia pastoris. Preparative Biochemistry & Biotechnology. 2016, 27:1-7

8.Xiaolong Wang, Qi Wang, Jinjia Wang, Peng Bai, Lei Shi, Wei Shen, Mian Zhou, Xiangshan Zhou, Yuanxing Zhang, Menghao Cai*. Mit1 Transcription Factor Mediates Methanol Signaling and Regulates Alcohol Oxidase 1 Promoter in Pichia pastoris. Journal of Biological Chemistry. 2016, 291:6245-6261

9.Xiaoxu Zhang, Hao He, Ying Yin, Weiqiang Zhou, Menghao Cai*,Xiangshan Zhou, Yuanxing Zhang. A light–dark shift strategy derived from light-responded metabolic behaviors for polyketides production in marine fungus Halorosellinia sp.. Journal of Biotechnology. 2016, 221:34-42

10.Chu Shen, Ning Xu, Yanyun Gao, Xiaoyue Sun, Ying Yin*, Menghao Cai*, Xiangshan Zhou, Yuanxing Zhang. Stimulatory effect of ethanol on libertellenone H biosynthesis by Arctic fungus Eutypella sp. D-1. Bioprocess and Biosystem Engineering. 2016, 39:353360

11.Xiaolong Wang, Menghao Cai*, Lei Shi, Qi Wang, Jinxiang Zhu, Jinjia Wang, Mian Zhou, Xiangshan Zhou, Yuanxing Zhang. PpNrg1 is a transcriptional repressor for glucose and glycerol repression of AOX1 promoter in methylotrophic yeast Pichia pastoris. Biotechnology Letters. 2016, 38:291-298.

12.Tao Jiang, Menghao Cai*, Mengmeng Huang, Hao He, Jian Lu, Xiangshan Zhou, Yuanxing Zhang. Characterization of a thermostable raw-starch hydrolyzing α-amylase from deep-sea thermophile Geobacillus sp. Protein Expression and Purification. 2015, 114: 15-22

13.Yingwei Liu, Xiangshan Zhou, Zhiwei Song, Yuanxing Zhang*. Sodium butyrate enhances the acidic isoform content of recombinant human erythropoietin produced by Chinese hamster ovary cells. Biotechnology Letters. 2014, 36(5): 907-911

14.John S. Y. Goh, Yingwei Liu, Haifeng Liu, Kah Fai Chan, Corrine Wan, Gavin Teo, Xiangshan Zhou, Fusheng Xie, Peiqing Zhang, Dr. Yuanxing Zhang, Dr. Zhiwei Song*. Highly sialylated recombinant human erythropoietin production in large-scale perfusion bioreactor utilizing CHO-gmt4 (JW152) with restored GnT I function. 2014, 9(1): 100-109

15.Zhenzhong Yu, Menghao Cai*, Wei Hu, Ying Zhang, Jiao Zhou, Xiangshan Zhou*,Yuanxing Zhang. A cyclin-like protein, ClgA, regulates development in Aspergillus nidulans. Research in Microbiology. 2014, 165(6): 462-467

16.Haifeng Liu, Xiangshan Zhou*, Shousheng Tian, Xianghui Hao, Jinhua You, Yuanxing Zhang* Two-step transpeptidation of the insulin precursor expressed in Pichia pastoris to insulin ester via trypsin-catalyzed cleavage and coupling. Biotechnology and Applied Biochemistry. 2014, 61(4): 408-417

17.Menghao Cai†, Ying Zhang†, Wei Hu, Wei Shen, Zhenzhong Yu, Weiqiang Zhou, Tao Jiang, Xiangshan Zhou* and Yuanxing Zhang. Genetically shaping morphology of the filamentous fungus Aspergillus glaucus for production of antitumor polyketide aspergiolide A. Microbial Cell Factories 2014 13:73

18.Weiqiang Zhou, Menghao Cai*, Ke Na, Chu Shen, Xiaoxu Zhang, Xiangshan Zhou, Wenjie Zhao, Yuanxing Zhang. pH-dependent accumulation of anticancer compound on mycelia in fermentation of marine fungus. Journal of Industrial Microbiology & Biotechnology. 2014, 41: 1169-1173

19.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. 2014, 37:575-584

20.Pham Ngoc Tu, Yamin Wang, Menghao Cai, Xiangshan Zhou*, Yuanxing Zhang*. Co-expressions of Protein Tyrosine Kinases EGFR-2 and PDGFRβ with Protein Tyrosine Phosphatase 1B in Pichia pastoris. Journal of Microbiology and Biotechnology, 2014, 24(2):152–159

21.Limei Gao, Menghao Cai*, Wei Shen, Siwei Xiao, Xiangshan Zhou, Yuanxing Zhang. Engineered fungal polyketide biosynthesis in Pichia pastoris: a potential excellent host for polyketide production. Microbial Cell Factories 2013, 12:77

22.Weiqiang Zhou, Menghao Cai*, Jiushun Zhou, Tao Jiang, Jiao Zhou, Meixia Wang, Xiangshan Zhou*, Yuanxing Zhang. Nutrition and bioprocess development for efcient biosynthesis of an antitumor compound from marine-derived fungus. Journal of Industrial Microbiology & Biotechnology. 2013, 40:1131-1142

23.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

24.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, 58: 537-546

25.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

26.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

27.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

28.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

29.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

30.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

31.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.

32.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.

33.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

34.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.

35.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

36.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

37.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

38.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

39.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 insert4domain receptor (KDR) in the peroxisomes of Pichia pastoris. FEMS Yeast Research, 2009, 9: 732-741

40.Pin Lv, Xiangshan Zhou*, Jinhua You, Bang-Ce Ye, and Yuanxing Zhang. Extraction of trace amount of severely degraded DNA. Zeitschrift fur Naturforschung C (Z. Naturforsch. C), 2009, 64c: 581-589

41.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

42.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

43.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

44.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

45.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

46.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


  

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