周祥山 - 华东理工大学 - 生物工程学院

个人简介

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”。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。

研究领域

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。

近期论文

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