生物医药

应用微生物选育、工业微生物代谢工程育种、工业/食品用酶开发等

1. Zhang XianΔ, Zhang RongzhenΔ, Bao Teng, Rao Zhiming, Yang Taowei, Xu Meijuan, Xu Zhenghong, Li Huazhong, Yang Shangtian. The rebalanced pathway significantly enhances acetoin production by disruption of acetoin reductase gene and moderate-expression of a new water-forming NADH oxidase in Bacillus subtilis [J]. Metabolic Engineering. 23: 34-41, 2014.
2. Zhang Xian, Rao Zhiming*, Li Jingjing, Zhou Junping, Yang Taowei, Xu Meijuan, Bao Teng, Zhao Xiaojing. Improving the acidic stability of Staphylococcus aureus α acetolactate decarboxylase in Bacillus subtilis by changing basic residues to acidic residues [J]. Amino Acids. 47(4):707–717, 2015.
3. Song Liu, Xian Zhang, Fei Liu, Meijuan Xu, Taowei Yang, Mengfei Long, Junping Zhou, Tolbert Osire, Shangtian Yang, Zhiming Rao. Designing of a Cofactor Self-Sufficient Whole-Cell Biocatalyst System for Production of 1,2-Amino Alcohols from Epoxides. ACS Synthetic Biology. 2019, 8:734-743.
4. Xian Zhang, Rumeng Han, Teng Bao, Xiaojing Zhao, Xiangfei Li, Manchi Zhu, Taowei Yang, Meijuan Xu, Minglong Shao, Youxi Zhao, Zhiming Rao. Synthetic engineering of Corynebacterium crenatum to selectively produce acetoin or 2,3-butanediol by one step bioconversion method. Microbial Cell Factories. 2019, 18:128.
5. Xian Zhang, Manchi Zhu, Rumeng Han, Youxi Zhao, Kewei Chen, Kai Qian, Minglong Shao, Taowei Yang, Meijuan Xu, Jianzhong Xu, Zhiming Rao. A novel 3-phytosterone-9α-hydroxylase oxidation subunit and its application in bioconversion of 4-androstene-3,17-dione to 9α-hydroxy-4-androstene-3,17-dione coupling with a NADH regeneration formate dehydrogenase. Molecules. 2019, 24(14):2534.
6. Zhang XianΔ, Bao TengΔ, Rao Zhiming, Yang Taowei, Xu Zhenghong, Yang Shangtian, Li Huazhong. Two-stage pH Control Strategy Based on The pH Preference of Acetoin Reductase Regulates Acetoin and 2,3-butanediol Distribution in Bacillus subtilis [J]. PLoS One. 9(3): e91187, 2014.
7. Zhang Xian, Zhang Rongzhen*, Bao Teng, Yang Taowei, Xu Meijuan, Li Huazhong, Xu Zhenghong, Rao Zhiming*. Moderate expression of the transcriptional regulator ALsR enhances acetoin production by Bacillus subtilis [J]. J Ind Microbiol Biotechnol. 40(9):1067-1076, 2013.
8. Zhang Xian, Yang Taowei, Lin Qing, Xu Meijuan, Xia Haifeng, Xu Zhenghong, Li Huazhong, Rao Zhiming*. Isolation and identification of an acetoin high production bacterium that can reverse transform 2,3-butanediol to acetoin at the decline phase of fermentation [J]. World J Microbiol Biotechnol. 27(12):2785-2790, 2011.
9. Zhang Xian, Zhang Rongzhen*, Yang Taowei, Zhang Jing, Xu Meijuan, Li Huazhong, Xu Zhenghong, Rao Zhiming*. Mutation breeding of acetoin high producing Bacillus subtilis blocked in 2,3-butanediol dehydrogenase [J]. World J Microbiol Biotechnol. 29: 1783-1789, 2013.
10. Xian Zhang, Zhiming* R, Zhang L, Meijuan X, Taowei Y. Efficient 9α-hydroxy-4-androstene-3,17-dione production by engineered Bacillus subtilis co-expressing Mycobacterium neoaurum 3-ketosteroid 9α-hydroxylase and B. subtilis glucose 1-dehydrogenase with NADH regeneration. SpringerPlus. 5:1207, 2016.
11. Xian Zhang, Dan Wu, Taowei Yang, Meijuan Xu, Zhiming Rao*. Over-expression of Mycobacterium neoaurum 3-ketosteroid-Δ1-dehydrogenase in Corynebacterium crenatum for efficient bioconversion of 4-androstene-3,17-dione to androst-1,4-diene-3,17-dione. Electronic Journal of Biotechnology. 2016, 24: 84-90.
12. Zhang, Xian, Zhi Wang, Yimai Wang, Xu Li, Manchi Zhu, Hengwei Zhang, Meijuan Xu, Taowei Yang, and Zhiming Rao*. Heterologous Expression and Rational Design of l-asparaginase from Rhizomucor miehei to Improve Thermostability. Biology. 2021; 10(12):1346.
13. Zhang, Xian, Ruiqi Lu, Qiang Wang, Mengkai Hu, Zhiyue Li, Meijuan Xu, Taowei Yang, Rongzhen Zhang*, and Zhiming Rao*. Production of d-Tagatose by Whole-Cell Conversion of Recombinant Bacillus subtilis in the Absence of Antibiotics. Biology. 2021; 10(12):1343.
14. Qiang WangΔ, Xian ZhangΔ, *, Kexin Ren, Rumeng Han, Ruiqi Lu, Teng Bao, Xuewei Pan, Taowei Yang, Meijuan Xu, and Zhiming Rao*.Acetoin production from lignocellulosic biomass hydrolysates with a modular metabolic engineering system in Bacillus subtilis. Biotechnology for Biofuels and Bioproducts.15, 87 (2022).
15. Teng BaoΔ, Xian ZhangΔ, Xiaojing Zhao, Zhiming Rao, Taowei Yang，Shangtian Yang. Regulation of the NADH pool and NADH/NADPH ratio redistributes acetoin and 2,3-butanediol proportion in Bacillus subtilis. Biotechnology Journal, 8(10): 1298-1306, 2015.
16. Bao TengΔ, Zhang XianΔ, Rao Zhiming, Zhao Xiaojing, Zhang Rongzhen, Yang Taowei, Xu Zhenghong, Yang Shangtian. Efficient whole-cell biocatalyst for acetoin production with NAD+ regeneration system through homologous co-expression of 2,3-butanediol dehydrogenase and NADH oxidase in engineered Bacillus subtilis. PLoS One, 9(7): e102951, 2014.
17. Xu Li, Xian Zhang, Shuqin Xu, Meijuan Xu, Taowei Yang, Li Wang, Huiling Zhang, Haitian Fang, Tolbert Osire, Zhiming Rao.Insight into the thermostability of thermophilic L-asparaginase and non-thermophilic L-asparaginase II through bioinformatics and structural analysis. Applied Microbiology and Biotechnology. 2019, 103(17):7055-7070
18. Xian Zhang, Zhaoyang Xu, Song Liu, Kai Qian, Meijuan Xu, Taowei Yang, Jianzhong Xu, Zhiming Rao. Improving the Production of Salt-Tolerant Glutaminase by Integrating Multiple Copies of Mglu into the Protease and 16S rDNA Genes of Bacillus subtilis 168. Molecules. 2019, 24(3):592.
19. Chunlin Tan, Xian Zhang, Zhijing Zhu, Meijuan Xu, Taowei Yang, Tolbert Osire, Shangtian Yang, Zhiming Rao. Asp305Gly mutation improved the activity and stability of the styrene monooxygenase for efficient epoxide production in Pseudomonas putida KT2440. Microbial Cell Factories. 2019, 18(12):14.
20. Xu Li, Shuqin Xu, Xian Zhang, Meijuan Xu, Taowei Yang, Li Wang, Huiling Zhang, Haitian Fang, Tolbert Osire, Shangtian Yang, Zhiming Rao. Design of a high-efficiency synthetic system for l-asparaginase production in Bacillus subtilis. Engineering in Life Sciences. 2019, 19(3):229-239.

获授权国际发明专利
1. Zhiming Rao, Junxian Zheng, Meijuan Xu, Taowei Yang, Xian Zhang. Signal peptide, L-glutamic acid synthesized using konjac flour and methods of using same. United States Patent, No.: US 10329592 B2, 2019.
2. Zhiming Rao, Zaiwei Man, Meijuan Xu, Taowei Yang, Xian Zhang. Method for increasing yield of L-arginine by knocking out flavin reductases. United States Patent, No.: US 10465218 B2, 2019.
获授权国家发明专利（5项代表作）：
1. 张显， 饶志明， 李谞， 杨套伟， 徐美娟， 张恒维， 赵浩东， 刘鹏。一种L-天冬酰胺酶突变体及其构建方法。中国发明专利，授权号：ZL2017113289780
2. 张显， 饶志明， 杨套伟， 徐美娟， 韩如梦。一种稳定性提高的NADH氧化酶及其在乙偶姻生产中的应用。中国发明专利，授权号：ZL201711323996X
3. 饶志明，张显，杨套伟，徐美娟，李静静，张静，刘俊佳。利用调控蛋白ALsR适度加强枯草芽孢杆菌乙偶姻合成。中国发明专利，授权号： ZL20120360503.0.
4. 饶志明，杨套伟，张显，徐美娟，满在伟。利用一株安全菌株发酵生物柴油副产物粗甘油生产2,3-丁二醇。中国发明专利，授权号：ZL201210360637.2
5. 饶志明，杨套伟，张显，徐美娟，满在伟。通过加强辅酶循环再生速率提高Bacillus amyloliquefaciens 2，3-丁二醇产量。中国发明专利，授权号：ZL201310342415.2
参与申报的国际专利（5项代表作）：
1. 饶志明，郑俊贤，徐美娟，杨套伟，张显。一种信号肽及其在利用魔芋粉合成L-谷氨酸及其高值化的应用。PCT/CN2015/095285
2. 饶志明，郑俊贤，徐美娟，杨套伟，张显。一种信号肽及其在利用魔芋粉合成L-精氨酸及其高值化的应用。PCT/CN2015/095286
3. 饶志明，王梅洲，徐美娟，张显，杨套伟。一种利用重组枯草芽孢杆菌全细胞转化生产L-鸟氨酸的方法。PCT/CN2015/094424
4. 饶志明，龙水清，张显，杨套伟，徐美娟。一种酶活提高的L-天冬酰胺酶突变体及其构建方法。PCT/CN2015/094554
5. 饶志明，邵明龙，张显，杨套伟，徐美娟。一种新金色分枝杆菌来源的甾酮C27-单加氧酶及其应用。PCT/CN2016/097110

1. 国家自然科学基金-面上项目：转录因子SctR调控氧化葡萄糖酸杆菌耐有机溶剂的分子机制解析及耐溶剂底盘细胞构建（32171471），2022.01-2025.12
2. 国家重点研发项目子课题：迭代提升细胞性能创建高产氨基酸菌种库（2021YFC2100903/003），2021.07-2025.06
3. 国家重点研发项目子课题：数字细胞驱动的性能模拟及测试应用2020YFA0908304/002，2020.11-2025.10
4. 国家自然科学基金-青年基金：Bacillus subtilis芽孢合成期乙偶姻合成代谢流重排研究（31500065），2016.1-2018.12
5. “863”项目“有机酸生物制造”子课题：α-氨基丁酸合成多酶催化体系协同调控与修饰（2015AA021004-4），2015.1-2017.12
6. 宁夏回族自治区重点研发项目：乳糖组分的生物转化技术研究与益生产品开发（2020BFH02011），2020.01-2023.12
7. 山东省重大科技创新工程项目：生物法高效制备高值化功能性碳水化合物生物催化剂工业属性强化（2019JZZY020605-2），2019.01-2021.12
8. 江苏省自然科学基金-青年基金：枯草芽孢杆菌细胞衰亡期乙偶姻合成调控研究（BK20150142），2015.7-2018.6
9. 中国博士后第9批特别资助：枯草芽孢杆菌芽孢形成期乙偶姻合成调控及分子机制研究（2016T90421），2016.1-2017.12
10. 企业合作横向项目：高产γ-氨基丁酸微生物菌株的筛选及功能强化（210864）2021.06-2022.12
11. 中国博士后第57批面上一等资助（2015M570407）：L-天冬酰胺酶热稳定性改造及分子机理研究，2015.1-2016.12

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