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****，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”。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:
<!--[if !supportLists]-->1.<!--[endif]-->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..
<!--[if !supportLists]-->2.<!--[endif]-->Jinjia Wang, Xiaolong Wang, Lei Shi, Fei Qi, Ping Zhang, Yuanxing Zhang, Xiangshan Zhou*, Zhiwei Song*, Menghao Cai*. Methanol-independent protein expression by AOX1promoter with trans-acting elements engineering and glucose-glycerol-shift induction in Pichia pastoris. Scientific Reports 2017, 7: 41850.
<!--[if !supportLists]-->3.<!--[endif]-->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 Geobacillussp. Food Biotechnology. 2017, 2017, 31(1): 57-71.
<!--[if !supportLists]-->4.<!--[endif]-->Ying Xue, Chuixing Kong, Wei Shen, Chenxiao Bai, Yanna Ren, Xiangshan Zhou, Yuanxing Zhang, Menghao Cai*. Methylotrophic yeast Pichia pastorisas a chassis organism for polyketide synthesis via the full citrinin biosynthetic pathway. Journal of Biotechnology. 2017, 242:64-72
<!--[if !supportLists]-->5.<!--[endif]-->Shaomei Liu, Jiaxin Li, Yuan Wu, Yanna Ren, Qi Liu, Qiyao Wang, Xiangshan Zhou, Menghao Cai*, Yuanxing Zhang. De novotranscriptome sequencing of marine-derived Aspergillus glaucusand comparative analysis of metabolic and developmental variations in response to salt stress. Genes & Genomics. 2017, 39:317-329.
<!--[if !supportLists]-->6.<!--[endif]-->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
<!--[if !supportLists]-->7.<!--[endif]-->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
<!--[if !supportLists]-->8.<!--[endif]-->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 1Promoter in Pichia pastoris. Journal of Biological Chemistry. 2016, 291:6245-6261
<!--[if !supportLists]-->9.<!--[endif]-->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 Haloroselliniasp.. Journal of Biotechnology. 2016, 221:34-42
<!--[if !supportLists]-->10.<!--[endif]-->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 Eutypellasp. D-1. Bioprocess and Biosystem Engineering. 2016, 39:353?360
<!--[if !supportLists]-->11.<!--[endif]-->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 AOX1promoter in methylotrophic yeast Pichia pastoris. Biotechnology Letters. 2016, 38:291-298.
<!--[if !supportLists]-->12.<!--[endif]-->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
<!--[if !supportLists]-->13.<!--[endif]-->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
<!--[if !supportLists]-->14.<!--[endif]-->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
<!--[if !supportLists]-->15.<!--[endif]-->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
<!--[if !supportLists]-->16.<!--[endif]-->Haifeng Liu, Xiangshan Zhou*, Shousheng Tian, Xianghui Hao, Jinhua You, Yuanxing Zhang* Two-step transpeptidation of the insulin precursor expressed in Pichia pastoristo insulin ester via trypsin-catalyzed cleavage and coupling. Biotechnology and Applied Biochemistry. 2014, 61(4): 408-417
<!--[if !supportLists]-->17.<!--[endif]-->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 glaucusfor production of antitumor polyketide aspergiolide A. Microbial Cell Factories 2014 13:73
<!--[if !supportLists]-->18.<!--[endif]-->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
<!--[if !supportLists]-->19.<!--[endif]-->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 Vibriosp. QY102. Bioprocess and Biosystem Engineering. 2014, 37:575-584
<!--[if !supportLists]-->20.<!--[endif]-->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
<!--[if !supportLists]-->21.<!--[endif]-->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
<!--[if !supportLists]-->22.<!--[endif]-->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
<!--[if !supportLists]-->23.<!--[endif]-->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
<!--[if !supportLists]-->24.<!--[endif]-->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
<!--[if !supportLists]-->25.<!--[endif]-->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
<!--[if !supportLists]-->26.<!--[endif]-->ChuanpengNiu, MenghaoCai, YuanxingZhang, XiangshanZhou*. Biosynthetic origin of the carbon skeleton of a novel anti-tumorcompound, haloroquinone, from amarine-derivedfungus, Haloroselliniasp. Biotechnology Letters, 2012, 34: 2119-2124
<!--[if !supportLists]-->27.<!--[endif]-->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. JournalofAppliedGenetics. 2012, 53(3): 355~362
<!--[if !supportLists]-->28.<!--[endif]-->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 glaucusfor the production of Anti-cancer polyketide. Marine Biotechnology. 2012, 14: 665-671
<!--[if !supportLists]-->29.<!--[endif]-->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
<!--[if !supportLists]-->30.<!--[endif]-->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
<!--[if !supportLists]-->31.<!--[endif]-->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.
<!--[if !supportLists]-->32.<!--[endif]-->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 fungusAspergillus glaucusby oxygen carrier addition and impeller combination in a bioreactor. Bioresource Technology, 2011, 102: 3584-3586.
<!--[if !supportLists]-->33.<!--[endif]-->Ping Zhang, Wenwen Zhang, Xiangshan Zhou*, Peng Bai, James M. Cregg, Yuanxing Zhang*. Catabolite repression of Aox in Pichia pastorisis dependent on hexose transporter PpHxt1 and Pexophagy. Applied and Environmental Microbiology, 2010, 76(18): 6108-6118
<!--[if !supportLists]-->34.<!--[endif]-->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.
<!--[if !supportLists]-->35.<!--[endif]-->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
<!--[if !supportLists]-->36.<!--[endif]-->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
<!--[if !supportLists]-->37.<!--[endif]-->Yaoji Xuan, Xiangshan Zhou*, Wenwen Zhang, Xiao Zhang, Zhiwei Song, Yuanxing Zhang. An upstream activation sequence control the expression of AOX1gene in Pichia pastoris. FEMS Yeast Research, 2009, 9: 1271-1282
<!--[if !supportLists]-->38.<!--[endif]-->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
<!--[if !supportLists]-->39.<!--[endif]-->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
<!--[if !supportLists]-->40.<!--[endif]-->Pin Lv, Xiangshan Zhou*, Jinhua You, Bang-Ce Ye, and Yuanxing Zhang. Extraction of trace amount of severely degraded DNA. Zeitschrift fur NaturforschungC (Z. Naturforsch. C), 2009, 64c: 581-589
<!--[if !supportLists]-->41.<!--[endif]-->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 glaucusby feeding of biosynthetic precursors and inhibitors simultaneously. Bioresource Technology, 2009, 100(18): 4244-4251
<!--[if !supportLists]-->42.<!--[endif]-->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 glaucusvia the polyketide pathway. Tetrahedron Letters, 2009, 50 (9): 1082–1085
<!--[if !supportLists]-->43.<!--[endif]-->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
<!--[if !supportLists]-->44.<!--[endif]-->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
<!--[if !supportLists]-->45.<!--[endif]-->Lin Chen, Xiangshan Zhou*, Weimin Fan and Yuanxing Zhang. Expression, purification and characterization of a recombinant Lipomyces starkeydextranase in Pichia pastoris.Protein Expression and Purification, 2008, 58: 87-93
<!--[if !supportLists]-->46.<!--[endif]-->Chun Wei, Xiangshan Zhou, Yuanxing Zhang*. Improving intracellular production of recombinant protein in Pichia pastorisusing an optimized preinduction glycerol-feeding scheme. Applied Microbiology and Biotechnology, 2008, 78: 257-264




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E-mail:xszhou@ecust.edu.cn