蔡孟浩
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:1549

蔡孟浩

生物化工专业:硕士生导师

生物工程专业:硕士生导师

生物工程领域:工程硕士导师


  

男,博士,副教授,华东理工大学生物工程学院。2006年毕业于华东理工大学理工优秀生部,获工学学士学位;2009-2010年英国布里斯托大学化学院联合培养博士生;2011年获得华东理工大学生物化工博士学位。曾获得上海市研究生创新计划基金、生物工程学院第一届青年教师远志计划基金资助。2011-2014年,华东理工大学师资博士后、助理研究员,2014年任职副教授。目前,担任中国微生物学会海洋微生物学专业委员会委员(2016-2021年),第四届中国生物化学与分子生物学学会海洋生物化学与分子生物学分会理事(2016-2020年),中国医学会海洋药物专业委员会中国海洋药物博士论坛青年委员会委员(2015-2019年)。

作为项目负责人,主持国家自然科学基金、国家863课题、中央高校基本科研业务费专项基金、上海科技创新行动计划项目(基础领域)、国家重大新药创制合作课题、企业横向合作项目等多项课题。在Metabolic EngJ Biol ChemSci RepMicrob Cell FactJ BiotechnolBioresourc Technol等权威期刊发表SCI论文40余篇,第一或通讯作者30余篇。申请中国发明专利14项,已授权6项。担任Microb Cell FactAppl Microbiol BiotechnolBiotechnol LettFEMS Yeast ResAppl Biochem BiotechnolBiochem Eng J等杂志审稿人。主讲本科生抗体工程课程,研究生基因工程制药课程,参讲博士生微生物细胞信号转导课程。

  

研究方向:

1. 药物化合物的合成生物学与代谢工程:运用分子生物学及组合生物化学手段,同源改造生产菌株的代谢网络,或异源(大肠杆菌、酵母、米曲霉)重建产物合成途径,并通过组合静态控制、生物传感元件设计及动态控制,实现小分子药物化合物(如真菌聚酮药物)在微生物细胞工厂中的高效合成。

2. 新型底盘细胞的分子设计与优化:以毕赤酵母为对象,解析相关启动子的转录调控机制,并运用合成生物学策略重设计转录调控网络,解决碳源和前体阻遏问题,优化途径节点关键酶的表达,平衡代谢网络,重塑新型高效底盘细胞,用于药用蛋白及小分子药物化合物的高效合成。

3. 药物化合物的发酵工程:针对药品及食品工业的重要菌属——霉菌,通过菌丝形态调控、合成途径分析及调控、发酵工程优化与控制,大幅提高霉菌生产药物化合物的能力,并通过发酵放大建立中试发酵工艺。

  

教育经历:

2009.10-2010.10   英国布里斯托大学有机与生物化学联合培养博士

2006.9-2011.3     华东理工大学生物化工博士

2002.9-2006.6     华东理工大学理工优秀生部学士

  

工作经历:

2014.9-至今,华东理工大学副教授,生物工程学院

2013.8-2014.8,华东理工大学助理研究员,生物工程学院

2011.7-2013.7,华东理工大学师资博士后,生物工程学院/药学院

  

承担及参与项目:

2017-2018,大肠杆菌发酵工艺开发(企业合作项目-细胞治疗质粒规模化制备);

2017-2020,甲醇酵母cPAOX1-TF(AD)转录调控器件库构建及生物合成系统设计(上海科技创新行动计划基础研究领域项目,负责人);

2017-2019,从基因到分子:深海微生物稀有药源产物的生物合成(生工学院远志计划,负责人);

2015-2017,剪切敏感型霉菌菌丝形成特异性基因发掘及发酵应用(中央高校基本科研业务费专项基金,负责人);

2014-2016,盐度胁迫调控海洋灰绿曲霉发育转变的分子机制研究(国家自然科学基金青年基金,负责人);

2012-2015,极地药源微生物活性产物的规模化发酵与制备(国家863项目子课题,负责人);

2012-2015,海洋抗肿瘤候选药物SZ-685C的发酵优化及制备(国家重大新药专项课题合作课题,负责人);

2012-2016,剪切敏感型霉菌的理性选育和形态塑造及其在发酵中的应用(国家自然科学基金面上项目,课题骨干成员);

2011-2014,海洋微生物大规模发酵制备候选药物关键技术(国家863主题项目,课题骨干成员)

  

代表性论文(*通讯作者,#共同第一)

1.KongC, Huang H, Xue Y, Liu Y, Peng Q, Liu Q, Yin Y, Zhou X, Zhang Y, Cai M*. Heterologous pathway assembly reveals molecular steps of fungal terreic acid biosynthesis. 2018,Sci Rep.accepted.

2.Liu Y, Tu X, Xu Q, Bai C, Kong C, Liu Q, Yu J, Peng Q, Zhou X, Zhang Y, Cai M*. Engineered monoculture and co-culture of methylotrophic yeast for de novo production of monacolin J and lovastatin from methanol. Metab Eng. 2018, 45:189-199.

3. Wang J, Wang X, Shi L, Qi F, Zhang P, Zhang Y, Zhou X*, Song Z*, Cai M*. Methanol-independent protein expression by AOX1 promoter with trans-acting elements engineering and glucose-glycerol-shift induction in Pichia pastoris.Sci Rep. 2017, 7:41850.

4. Wang X, Wang Q, Wang J, Bai P, Shi L, Shen W, Zhou M, Zhou X, Zhang Y, Cai M*. Mit1 transcription factor mediates methanol signaling and regulates alcohol oxidase 1promoter in Pichia pastoris. J Biol Chem. 2016, 291:6245-6261.

5. Xue Y, Kong C, Shen W, Bai C, Ren Y, Zhou X, Zhang Y, Cai M*. Methylotrophic yeast Pichia pastoris as a chassis organism for polyketide synthesis via the full citrinin biosynthetic pathway. J Biotechnol. 2017, 242:64-72.

6. Zhang X, He H, Yin Y, Zhou W, Cai M*, Zhou X, Zhang Y. A light–dark shift strategy derived from light-responded metabolic behaviors for polyketides production in marine fungus Halorosellinia sp.. J Biotechnol. 2016, 221:34-42.

7. Cai M#, Zhang Y#, Hu W, Shen W, Yu Z, Zhou W, Jiang T, Zhou X*, Zhang Y. Genetically shaping morphology of the filamentous fungus Aspergillus glaucus for production of antitumor polyketide aspergiolide A. Microb Cell Fact. 2014, 13:73.

8. Yu Z, Cai M*, Hu W, Zhang Y, Zhou J, Zhou X, Zhang Y. A cyclin-like protein, ClgA, regulates development in Aspergillus nidulans. Res Microbiol. 2014, 165:462-467.

9. Gao L, Cai M*, Shen W, Xiao S, Zhou X, Zhang Y. Engineered fungal polyketide biosynthesis in Pichia pastoris: a potential excellent host for polyketide production.Microb Cell Fact. 2013, 12:77.

10. Zhou W, Cai M*, Zhou J, Jiang T, Zhou J, Wang M, Zhou X*, Zhang Y. Nutrition and bioprocess development for efficient biosynthesis of an antitumor compound from marine-derived fungus.J Ind Microbiol Biotechnol. 2013, 40:1131-1142.

11. Davison J, al Fahad A, Cai M, Song Z, Yehia SY, Lazarus CM, Bailey AM, Simpson TJ, Cox RJ.Genetic, molecular, and biochemical basis of fungal tropolone biosynthesis.Proc Natl Acad Sci U S A. 2012, 109: 7642-7647.

12. Cai M, Zhou X, Lu J, Fan W, Zhou J, Niu C, Kang L, Sun X, Zhang Y.An integrated control strategy for the fermentation of the marine-derived fungus Aspergillus glaucus for the production of anti-cancer polyketide. Mar Biotechnol. 2012, 14:665-671.

13. Cai M, Zhou X, Lu J, Fan W, Niu C, Zhou J, Sun X, Kang L, Zhang Y.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. Bioresourc Technol. 2011, 102: 3584-3586.

14. Cai M, Zhou X, Zhou J, Niu C, Kang L, Sun X, Zhang Y.Efficient strategy for enhancing aspergiolide A production by citrate feedings and its effects on sexual development and growth of marine-derived fungus Aspergillus glaucus. Bioresourc Technol. 2010, 101:6059-6068.

其他论文(*通讯作者,#共同第一)

15. Wang J, Wang X, Shi L, Zhang Y, Zhou X*, Cai M*.Reduced methanol input induces increased protein output by AOX1promoter in a trans‑acting elements engineered Pichia pastoris. J Ind Microbiol Biotechnol.2018, 45:25-30.

16. WuY, Ren Y, Zhou X, Cai M*, Zhang Y*. Transcription factor Agseb1 affects development, osmotic stress response, and secondary metabolism in marine-derived Aspergillus glaucus.J. Basic Microbiol.2017, 57:873-882 (cover article).

17. Shi L, Wang X, Wang J, Zhang P, Qi F, Cai M*, Zhang Y, Zhou x*. Transcriptome analysis of Δmig1Δmig2 mutant reveals their roles in methanol catabolism, peroxisome biogenesis and autophagy in methylotrophic yeast Pichia pastoris. accepted.

18. Huang M, Gao Y, Zhou X, Zhang Y, Cai M*. Regulating unfolded protein response activator HAC1p for production of thermostable raw-starch hydrolyzing α-amylase in Pichia pastoris.Bioproc. Biosyst. Eng.2017, 40:341-350.

19. Gao Y, Huang M, Sun X, Zhang X, Zhang Y, Zhou X*, Cai M*. Single-site mutation of C363G or N463T strengthens thermostability improvement of IG181-182 deleted acidic α-amylase from deep-sea thermophile Geobacillus sp. Food Biotechnol. 2017, 31:57-71.

20. Xiao S, Gao Y, Wang X, Shen W, Wang J, Zhou X, Cai M*, Zhang. Peroxisome-targeted and tandem repeat multimer expressions of human antimicrobial peptide LL37 in Pichia pastoris. Prep. Biochem. Biotechnol. 2017, 47:229-235.

21. Liu S, Li J, Wu Y, Ren Y, Liu Q, Wang Q, Zhou X, Cai M*, Zhang Y. De novo transcriptome sequencing of marine-derived Aspergillus glaucus and comparative analysis of metabolic and developmental variations in response to salt stress. Gen. Genom. 2017, 39:317-329.

22. He H, Xue Y, Xu N, Yin Y, Lu J, Cai M*, Zhang Y. A novel pH–precursor–glucose synergic control strategy for dinactin biosynthesis by an arctic actinomycete Streptomyces sp. Process Biochem. 2016, 2016, 51:1911-1918.

23. Shen C, Xu N, Gao Y, Sun X, Yin Y*, Cai M*, Zhou X, Zhang Y. Stimulatory effect of ethanol on libertellenone H biosynthesis by Arctic fungus Eutypella sp. D-1. Bioproc. Biosyst.Eng. 2016, 39:353-360.

24. Wang X,Cai M*, Shi L, Wang Q, Zhu J, Wang J, Zhou M, Zhou X, Zhang Y. PpNrg1 is a transcriptional repressor for glucose and glycerol repression of AOX1 promoter in methylotrophic yeast Pichia pastoris. Biotechnol. Lett. 2016, 38:291-298.

25. Wang M, He H, Na K, Cai M*, Zhou X, Zhao W, Zhang Y. Designing novel glucose/ornithine replenishment strategies by biosynthetic and bioprocess analysis to improve fibrinolytic FGFC1 production by the marine fungus Stachybotrys longispora. Process Biochem. 2015, 50:2012-2018

26. Jiang T, Cai M*, Huang M, He H, Lu J, Zhou X, Zhang Y. Characterization of a thermostable raw-starch hydrolyzing a-amylase from deep-sea thermophile Geobacillus sp. Protein Expres. Purif. 2015, 114:15-22.

27. Jiang T, Cai M*, Huang M, He H, Lu J, Zhou X, Zhang Y. Bioprocess exploration for thermostable α-amylase production of a deep-sea thermophile Geobacillus sp. in high temperature bioreactor. Prep. Biochem. Biotechnol. 2016, 46:620-627.

28. Zhou J, He H, Wang X, Lu J, Zhou X, Cai M*, Zhang Y. Optimization of nutrients for dinactin production by a marine Streptomyces sp. from the High Latitude Arctic. Biotechnol. Bioproc. Eng. 2015, 20:725-732.

29. Zhou W, Cai M*, Na K, Shen C, Zhang X, Zhou X, Zhao W, Zhang Y. pH-dependent accumulation of anticancer compound on mycelia in fermentation of marine fungus. J. Ind. Microbiol. Biotechnol. 2014, 41: 1169-1173.

30. Zhou J, Cai M*, Jiang T, Zhou W, Shen W, Zhou X, Zhang Y. Mixed carbon source control strategy for enhancing alginate lyase production by marine Vibrio sp. QY102. Bioproc. Biosyst. Eng. 2014, 37:575-584.

31. Gao L, Cai M*, Shen W, Xiao S, Zhou X, Zhang Y. Engineered fungal polyketide biosynthesis in Pichia pastoris: a potential excellent host for polyketide production. Microb. Cell Fact. 2013, 12:77.

32. Cai M, Fang Z, Niu C, Zhou X*, Zhang Y. Light regulation on growth, development and secondary metabolism of marine-derived filamentous fungi. Folia Microbiol. 2013, 58: 537-546.

33. Cai M, Sun X, Zhou X*, Zhang Y*. Roles of cobalt in biosynthesis stimulation of a cytotoxic compound from marine-derived Aspergillus glaucus. Process Biochemistry. 2012, 12: 2267–2274.

34.Cai M, Zhou X*, Sun X, Tao K, Zhang Y*. Statistical optimization of medium composition for aspergiolide A production by marine-derived fungus Aspergillus glaucus. J. Ind. Microbiol.Biotechnol. 2009, 36: 381-389.

35. Niu C, Cai M, Zhang Y, Zhou X*. Biosynthetic origin of the carbon skeleton of a novel anti-tumor compound, haloroquinone, from a marine-derived fungus, Halorosellinia sp. Biotechnol. Lett. 2012, 34:2119-2124.

36. Kang L, Cai M, Yu C, Zhang Y, Zhou X*. Improved production of the anticancer compound 1403C by glucose pulse feeding of marine Halorosellinia sp. (No. 1403) in submerged culture. Bioresourc. Technol.2011, 102:10750-10753.

37. Yu C, Cai M, Kang L, Zhang Y, Zhou X*. 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 Biochem.2012, 47:422-427.

38. Fang Z, Zhang Y, Cai M, Zhang J,Zhang Y, Zhou X*. Improved gene targeting frequency in marine-derived filamentous fungus Aspergillus glaucus by disrupting ligD. J.Appl. Genet.2012, 53:355–362.

39. Tu PG, Wang Y, Cai M, Zhou X*, Zhang Y*. Co-expressions of protein tyrosine kinases EGFR-2 and PDGFRβ with protein tyrosine phosphatase 1B in Pichia pastoris. J. Microbiol. Biotechnol.2014, 24: 152-159.

40. Wang S, Liu Q*, Cai M, Wang Q, Zhang Y. Fermentation preparation of recombinant Vibrio anguillarum vaccine with heterogeneous antigen display. Prep. Biochem. Biotechnol. 2013, 43:79-94.

41. Sun X, Zhou X*, Cai M, Tao K, Zhang Y*. 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. Bioresourc. Technol. 2009, 100: 4244-4251.

42. Sun X, Zhou X*, Cai M, Zhou J, Zhang Y*. Significant stimulation of o-phthalic acid in biosynthesis of aspergiolide A by a marine fungus Aspergillus glaucus. Bioresourc. Technol. 2010, 101: 3609-3616.

43. Tao K, Du L, Sun X, Cai M, Zhu T, Zhou X*, Gu Q, Zhang Y. Biosynthesis of aspergiolide A, a novel antitumor compound by a marine-derived fungus Aspergillus glaucus via the polyketide pathway. Tetra. Lett.2009, 50: 1082-1085.

44. Yin Y*, Cai M, Zhou X, Li Z, Zhang Y*. Polyketides in Aspergillus terreus: biosynthesis pathway discovery and application. Appl. Microbiol. Biotechnol. 2016, 100:7787-7798.

45. Shen W, Xue Y, Liu Y, Kong C, Wang X, Huang M, Cai M, Zhou X, Zhang Y, Zhou M*. A novel methanol-free Pichia pastoris system for recombinant protein expression. Microb. Cell Fact. 2016, 15:178.

46. Shen W, Kong C, Xue Y, Liu Y, Cai M, Zhang Y, Jiang T, Zhou X, Zhou M. Kinase screening in Pichia pastoris identified promising targets involved in cell growth and alcohol oxidase 1 promoter (PAOX1) regulation. PLoS ONE, 2016, DOI:10.1371/journal.pone.0167766.

47. Zhang X, GaoY, Yin Y*, Cai M, Zhou X, Zhang Y. Regulation of different polyketide biosynthesis by green light in an endophytic fungus of mangrove leaf. 3 Biotech.2017, 7:363.

48. Zhang X, GaoY, Yin Y*, Cai M, Zhou X, Zhang Y. Effective pH pretreatment and cell disruption method for real-time intracellular enzyme activity assay of a marine fungus covered with pigments. Prep. Biochem. Biotechnol.2017, 47:211-217.

49.李佳欣,刘绍梅,任燕娜,周祥山,蔡孟浩*,张元兴. 海洋灰绿曲霉AgveA基因响应盐度胁迫的功能分析. 华东理工大学学报(自然科学版).2017, 接收

50. 胡伟,李佳欣,李晓霞,蔡孟浩*,周祥山*,张元兴. 剪切敏感型海洋灰绿曲霉AgugtAAgugeA基因的克隆及功能分析. 华东理工大学学报(自然科学版). 2015, 41: 455-463.

51. 李晓霞, 蔡孟浩*, 胡伟, 李佳欣, 周祥山*, 张元兴. 海洋灰绿曲霉聚酮合酶基因的克隆与序列分析. 华东理工大学学报(自然科学版). 2014, 40: 579-585.

52. 齐飞, 蔡孟浩, 周祥山*, 张元兴. 基于rna-seq技术的毕赤酵母基因组重注释及新型强启动子的发现与序列分析. 华东理工大学学报(自然科学版). 2014, 40:167-175.

53. 柏鹏, 蔡孟浩, 周祥山*, 张元兴. 葡萄糖诱导型AOX1启动子毕赤酵母突变株B5的筛选. 工业微生物2013, 43: 69-72.

54. 牛传朋, 蔡孟浩, 李晓霞, 周祥山*, 张元兴. 海洋真菌Xylaria sp.(No.2508)生产xyloketal B的发酵优化.工业微生物 2012, 42:43-47.

55. 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.

56. 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.

  

专利:

蔡孟浩, 任燕娜, 周祥山, 张元兴. 生产胞磷胆碱的基因工程菌的构建与应用. 中国发明专利. 申请号201711180707.5.

蔡孟浩, 刘启, 周祥山, 张元兴. 无碳源阻遏毕赤酵母表达系统、其建立方法及应用. 中国发明专利. 申请号201710352843.1.

蔡孟浩, 刘一奇, 张元兴. 生产洛伐他汀及莫纳可林 J 的基因工程菌的构建与应用. 中国发明专利. 申请号201510552643.1.

蔡孟浩, 周久顺, 周祥山, 张元兴. 一种利用海洋弧菌生产褐藻胶裂解酶的方法. 中国发明专利. 专利号ZL201210068851.0.

蔡孟浩, 王美霞, 周祥山, 张元兴. 用于海洋长孢葡萄穗霉生产纤溶活性化合物的培养基. 中国发明专利.专利号ZL201310170435.6.

蔡孟浩, 周娇, 周祥山, 张元兴. 用于北极海洋放线菌Streptomyces sp.生产大环四重内酯类化合物的培养基. 中国发明专利. 申请号201310504941.4.

蔡孟浩, 沈处, 周祥山, 张元兴. 应用于北极丝状真菌生产二萜类化合物的发酵培养基. 中国发明专利. 申请号201510408258.X.

蔡孟浩, 沈处, 周祥山, 张元兴. 添加醇类促进二萜类化合物Libertellenone H产量的方法. 中国发明专利. 申请号201510408062.0.

张元兴, 蔡孟浩, 周祥山, 蒋涛, 黄猛猛. 一种耐高温淀粉酶、其编码基因及其应用. 中国发明专利. 申请号201410712820.3.

周祥山, 蔡孟浩, 张元兴, 孙学谦, 陶可敬, 范卫民, 陆健, 顾谦群, 朱天骄. 一种用于海洋灰绿曲霉生产新型抗肿瘤活性化合物的新型培养基及其制备方法. 中国发明专利, 专利号ZL200810038598.8.

周祥山, 周卫强, 蔡孟浩, 张元兴.利用海洋红树林内生真菌生产抗癌蒽醌类化合物的培养基及制备方法,中国发明专利, 专利号ZL201210067014.6.

周祥山, 蒋涛, 蔡孟浩, 张元兴.用于深海海洋嗜热细菌Geobacillus sp.生产淀粉酶的培养基.中国发明专利,专利号ZL201310169378.X.

周祥山, 蒋涛, 蔡孟浩, 张元兴.用于高密度培养深海海洋嗜热细菌Geobacillus sp.的培养基. 中国发明专利,专利号ZL201310170443.0.

周祥山, 周卫强. 蔡孟浩. 张元兴. 一种发酵培养海洋真菌生产抗癌化合物1403C的方法.中国发明专利. 申请号201310269533.5.

  

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