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:3077

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。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。

 获得上海市青年科技启明星计划,生物工程学院青年英才培养计划,上海市研究生创新计划资助。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),上海市生物工程学会合成生物学专业委员会委员(2018-2022年),中国药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,主持国家重点研发计划课题、国家自然科学基金、国家重大新药创制合作课题、国家863课题、上海科技创新行动计划项目、中央高校基本科研业务费专项基金、企业横向合作项目等多项课题。在Metabolic EngJ Biol ChemBiotechnol Biofuels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17项,已授权8项。担任Microb Cell FactAppl Microbiol BiotechnolFEMS Yeast ResBMCBiotechnolBiochem 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,参讲本科生分子生物学(英文)、博士生微生物细胞信号转导(英文)课程。


研究方向:

主要研究方向为微生物药物合成生物学,旨在利用异源底盘细胞重构天然药物合成途径或改造/调控原生宿主的药物合成途径,实现天然药物的微生物高效发酵生产,解决其来源受限、难制备、成本高等问题。

研究内容() 新型底盘细胞设计与检验:聚焦天然药物合成酶适配能力强的真核底盘宿主(酵母/曲霉),解析重要启动子的转录调控机制,以此挖掘特色生物元件并重构转录调控器件(),以此设计开发高效、多样化的正交/交互生物合成底盘系统,以满足天然药物生物合成中的不同需求。

研究内容() 药物分子生物合成与调控:运用分子生物学及组合生物化学手段,异源(酵母/曲霉)重构或同源(曲霉)改造/调控天然药物合成途径,设计组合静态控制及基于特色元/器件设计的动态控制策略,优化调控模式及平衡代谢网络,以此实现天然药物分子在微生物细胞工厂中的高效发酵生产。


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:

  1. 2019-2022,甲醇同化非交互菌群设计与药物合成应用(上海市青年科技启明星人才项目,负责人);

  2. 2019-2022,甲醇酵母正交/交互生物器件库设计与精细表达控制(国家自然科学基金项目,负责人);

  3. 2018-2021,黄芩素等黄酮的合成生物学制备体系研建(国家重点研发计划课题,子课题负责人);

  4. 2018-2021,极地微生物资源开发的发酵工艺研究(国家重点研发计划课题,负责人);

  5. 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,负责人);

  6. 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);

  7. 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);

  8. 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);

  9. 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);

  10. 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);

  11. 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);

  12. 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);

  13. 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)


发表论文(*通讯作者,#共同第一)

  1. XuQ, Bai C, Liu Y, Song L, Tian L, Yan Y, Zhou J, Zhou X, Zhang Y, Cai M*. Modulation of acetate utilization in Komagataella phaffii by metabolic engineering of tolerance and metabolism. Biotechnol Biofuels. 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. Kong C, 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. 2018:2116.

  4. Wang J, Wang X, Shi L, Zhang Y, Zhou X*, Cai M*. Reduced methanol input induces increased protein output by AOX1 promoter in a trans acting elements engineered Pichia pastoris. J Ind Microbiol Biotechnol. 2018, 45:25-30.

  5. 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. 2018, Gen. Genom. 40:399–412.

  6. Liu Y, Bai C, Xu Q, Zhou X, Zhang Y, Cai M*. Improved methanol derived lovastatin production through enhancement of the biosynthetic pathway and intracellular lovastatin efflux in methylotrophic yeast. Bioresour. Bioprocess. 2018,5:22

  7. 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.

  8. 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.

  9. Wu Y, 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).

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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 1 promoter in Pichia pastoris. J Biol Chem. 2016, 291:6245-6261.

  15. 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.

  16. 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, 51:1911-1918.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

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

  33. 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.

  34. 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.

  35. 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).20185(接收)

  36. 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.

  37. 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.

  38. Shi L, Wang J, Wang X, Zhang Y, Song Z, Cai M, Zhou X*. Transcriptome and metabolome analyses reveal global behaviour of a genetically engineered methanol-independent Pichia pastoris strain. Process Biochem. 2019, 76:46-54.

  39. Zhang X, Gao Y, 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.

  40. Zhang X, Gao Y, 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.

  41. 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.

  42. 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, 11:e0167766.

  43. 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.

  44. 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.

  45. 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.

  46. 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.

  47. 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.

  48. 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.

  49. 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.

  50. 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.

  51. 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.

  52. 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.

  53. 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.

  54. 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.

  55. 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.

  56. 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.

  57. 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.

  58. 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:

  1. 蔡孟浩, 刘一奇, 张元兴. 一种莫纳可林J异源生产的方法及应用. 申请号201810857983.9. 公开号108913732A.

  2. 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.公开号CN108424859A

  3. 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.公开号108949869A

  4. 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.

  5. 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.

  6. 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.

  7. 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. 专利号ZL201310504941.4.

  8. 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.公开号104962593A

  9. 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. 专利号201510408062.0.

  10. 蔡孟浩, 高燕云, 周祥山, 张元兴. 热稳定性提高的酸性淀粉酶突变体及其制备方法和应用. 申请号201610542505.X. 公开号CN108588057A

  11. 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.公开号105695435A.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.  

  17. 周祥山, 沈伟, 蔡孟浩, 张元兴.一种褐藻胶裂解酶基因algp及其制备方法与表达. 申请号201410353590.6. 公开号CN105296454 A.


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