简介

主要利用合成生物学技术进行模式工业微生物枯草芽孢杆菌底盘细胞的理性设计、复杂基因线路构建与动态代谢工程研究，包括代谢元件挖掘创制、代谢途径设计优化、代谢网络建模重构等，构建食品细胞工厂种子高效生产乳源关键活性组分(乳源蛋白、母乳低聚糖、脂溶性维生素、结构脂肪等)，部分产品如乙酰氨基葡萄糖、维生素K2、磷脂酰丝氨酸等已实现工业化生产，产生了显著的社会经济效益。以通讯作者在包括Nature Chemical Biology、Nucleic Acids Research、Nature Communications、Trends in Biotechnology等期刊发表SCI论文100余篇。主编出版5部中英文著作。

主要成果

一、论文（论著）发表情况

部分代表性论著如下：

1. Jiang Wei, Villamor David Hernandez, Peng Huadong, Chen Jian, Liu Long, Haritos Victoria, Ledesma-Amaro Rodrigo. Metabolic engineering strategies to enable microbial utilization of C1 feedstocks.Nature Chemical Biology. 2021,17: 845-855.

2. Deng Chen, Lv Xueqin, Li Jianghua, Zhang Hongzhi, Liu Yanfeng, Du Guocheng, Ledesma-Amaro Rodrigo, Liu Long. Synergistic improvement of N-acetylglucosamine production by engineering transcription factors and balancing redox cofactors.Metabolic Engineering. 2021,67: 330-346.

3. Xu Xianhao, Li Xueliang, Liu Yanfeng, Zhu Yonglian, Li Jianghua, Du Guocheng, Chen Jian, Ledesma- Amaro Rodrigo, Liu Long. Pyruvate-responsive genetic circuits for dynamic control of centralmetabolism.Nature Chemical Biology. 2020,16: 1261-1268.

4. Tian Rongzhen, Liu Yanfeng, Cao Yanting, Zhang Zhongjie, Li Jianghua, Liu Long, Du Guocheng, Chen Jian. Titrating bacterial growth and chemical biosynthesis for efficient N-acetylglucosamine and N-acetylneuraminic acid bioproduction.Nature Communications. 2020,11: 5078.

5. Wu Yaokang, Chen Taichi, Liu Yanfeng, Tian Rongzhen, Lv Xueqin, Li Jianghua, Du Guocheng, Chen Jian, Ledesma-Amaro Rodrigo, Liu Long. Design of a programmable biosensor-CRISPRi genetic circuits for dynamic and autonomous dual-control of metabolic flux inB. subtilis.Nucleic Acids Research. 2020,48: 996-1009.

6. Xu Xianhao, Liu Yanfeng, Du Guocheng, Ledesma-Amaro Rodrigo, Liu Long. Microbial chassis development for natural products biosynthesis.Trends in Biotechnology. 2020,38: 779-796.

7. Lv Xueqin, Zhang Cheng, Cui Shixiu, Xu Xianhao, Wang Lingling, Li Jianghua, Du Guocheng, Chen Jian, Ledesma-Amaro Rodrigo, Liu Long. Assembly of pathway enzymes by rationally engineering functional membrane microdomains for improved N-acetylglucosamine synthesis inBacillus subtilis.Metabolic Engineering. 2020,61: 96-105.

8. Lv Xueqin, Wu Yaokang, Tian Rongzhen, Gu Yang, Liu Yanfeng, Li Jianghua, Du Guocheng, Ledesma-Amaro Rodrigo, Liu Long. Synthetic metabolic channel by functional membrane microdomains for compartmentalized flux control.Metabolic Engineering. 2020,59: 106-118.

9. Lv Xueqin, Jin Ke, Wu Yaokang, Zhang Cheng, Cui Shixiu, Zhu Xiaonan, Li Jianghua, Du Guocheng, Liu Long. Enzyme assembly guided by SPFH-induced functional inclusion bodies for enhanced cascade biocatalysis.Biotechnology and Bioengineering. 2020,117: 1446-1457.

10. Deng Jieying, Chen Chunmei, Gu Yang, Lv Xueqin, Liu Yanfeng, Li Jianghua, Ledesma-Amaro Rodrigo, DuGuocheng, Liu Long. Creating an in vivo bifunctional gene expression circuit through an aptamer-based regulatory mechanism for dynamic metabolic engineering inBacillus subtilis.Metabolic Engineering. 2019,55: 179-190.

11. Gu Yang, Liu Yanfeng, Li Jianghua, Du Guocheng, Ledesma-Amaro Rodrigo, Liu Long. Synthetic redesign of central carbon and redox metabolism for high yield production of N-acetylglucosamine inBacillus subtilis.Metabolic Engineering. 2019,51: 59-69.

12. Deng Jieying, Gu Liuyan, Chen Taichi, Huang Hao, Yin Xiaoqiang, Lv Xueqin, Liu Yanfeng, Li Nan, Liu Zhenmin, Li Jianghua, Du Guocheng, Liu Long. Engineering the substrate transport and cofactor regeneration systems for enhancing 2’-fucosyllactose synthesis inBacillus subtilis.ACS Synthetic Biology. 2019,8: 2418-2427.

13. Wu Yaokang, Chen Taichi, Liu Yenfeng, Lv Xueqin, Li Jianghua, Du Guocheng, Ledesma-Amaro Rodrigo, Liu Long. CRISPRi allows optimal temporal control of N-acetylglucosamine bioproduction by a dynamic coordination of glucose and xylose metabolism inBacillus subtilis.Metabolic Engineering. 2018,49: 232-241.

14. Gu Yang, Xu Xianhao, Wu Yaokang, Niu Tengfei, Liu Yanfeng, Li Jianghua, Du Guocheng, Liu Long. Advances and prospects of Bacillus subtilis cellular factories: from rational design to industrial applications.Metabolic Engineering. 2018,50: 109-121.

15. Cui Shixiu, Lv Xueqin, Wu Yaokang, Li Jianghua, Du Guocheng, Ledesma-Amaro Rodrigo, Liu Long. Engineering a bifunctional Phr60-Rap60-Spo0A quorum-sensing molecular switch for dynamic fine-tuning of menaquinone-7 synthesis inBacillus subtilis.ACS Synthetic Biology. 2019,8: 1826-1837.

16. Deng Chen, Li Jianghua, Liu Yanfeng, Du Guocheng, Ledesma-Amaro Rodrigo, Liu Long. Synthetic repetitiveextragenic palindromic (REP) sequence as an efficient mRNA stabilizer for protein production and metabolic engineering in prokaryotic cells.Biotechnology and Bioengineering. 2019,116: 5-18.

17. Liu Yanfeng, Li Jianghua, Du Guocheng, Chen Jian, Liu Long. Metabolic engineering ofBacillus subtilisfueled by systems biology: recent advances and future directions.Biotechnology Advances. 2017,35: 20-30.

18. Liu Yanfeng, Link Hannes, Liu Long, Du Guocheng, Chen Jian, Sauer Uwe. A novel dynamic pathway analysis approachreveals a limiting futile cycle inN- acetylglucosamineoverproducingBacillus subtilis.Nature Communications. 2016,7:11933.

二、专利情况

获得中国授权发明专利50项，美国授权发明专利14项。部分美国授权发明专利如下：

1.Liu Long, Chen Jian, Du Guocheng, Li Jianghua, Niu Tengfei. Recombinant Bacillus subtilis for producing acetylglucosamine and construction method thereof.授权专利号：US 10, 093, 936.

2.Liu Long, Chen Jian, Du Guocheng, Yin Xian, Li Jianghua. Promoter and use thereof.授权专利号：US 9,926,569.

3.Liu Long, Chen Jian, Du Guocheng, Li Jianghua, Liu Yanfeng, Hannes Link, Uwe Sauer. Method for enhancingN-acetylglucosamine production through glck knockout ofBacillus subtilis.授权专利号：US 9,914,949.

4.Liu Long, Chen Jian, Du Guocheng, Yin Xian, Li Jianghua. Method of gene expression regulation.授权专利号：US 2018/0171344.

5.Liu Long, Chen Jian, Du Guocheng, Li Jianghua, Gu Yang, Song Yang, Deng Jieying, Zhao Yawen. Method for improving GlcNAc production of recombinant Bacillus subtilis.授权专利号：US 9,868,970.

6.Chen Jian, Du Guocheng, Liu Long, Li Jianghua, Guan Ningzi. Method for improving acid tolerance ofPropionibacterium acidipropionici.授权专利号：US 9,187,773.

7.Chen Jian, Du Guocheng, Li Jianghua, Liu Long, Feng Zhuolin. Method for increasing microbial catalase production授权专利号：US 8,722,364.

8.Liu Long, Li Jianghua, Niu Tengfei, Chen Jian, Du Guocheng. RecombinantBacillus subtilisfor increasing production of acetylglucosamine and construction method thereof.授权专利号：US 10,465,198.

三、承担教学科研项目情况

1.国家重点研发计划项目：数字细胞建模与人工模拟（2020YFA0908300，2020-2025年）

2.国家重点研发计划项目：高版本模式微生物底盘细胞（2018YFA0900300，2019-2024年）

3.国家重点研发计划课题：高版本大宗有机酸生产的丝状真菌底盘细胞构建（2018YFA0900504，2019-2024年）

4.国家基金委创新群体课题：食品微生物功能解析与利用（32021005，2021-2025年）

5.国家自然基金重点项目：枯草芽孢杆菌中母乳寡糖代谢网络的模块优化与动态调控（31930085，2020-2024年）

6.国家自然基金面上项目：基于乙酰辅酶A响应转录因子的双信号基因回路的计算设计与代谢调控（32070085，2021-2024年）

7.国家自然基金面上项目：由glmS核酶介导的枯草芽孢杆菌中N-乙酰氨糖代谢网络的动态优化调控(21676119,2017-2020年)

8.国家自然基金面上项目：基于枯草芽孢杆菌Spo0F-Spo0A双组分群体感应系统的维生素K2动态代谢调控(31871784，2019-2022年)

9.国家自然基金面上项目：克拉酸生物合成过程机制解析与代谢调控研究(31870069，2019-2022年)

10.国家自然基金面上项目：基于GlcNAc6P特异性磷酸酶定向筛选与进化的N-乙酰氨糖生物合成研究(31671845, 2017-2020年)

11.国家自然基金青年基金：基于枯草芽孢杆菌功能膜微域支架的N-乙酰氨基葡萄糖代谢调控研究(21808084，2019-2021年)

四、获奖情况（含指导学生获奖）

1.国家高层次人才特殊支持计划入选者(2020年)

2.科技部中青年创新人才(2020年)

3.江苏省科学技术奖励一等奖(2020年，排名第一)

4.第四届“闵恩泽能源化工奖”杰出贡献奖(2019年)

5.江苏省生物技术优秀青年学者奖(2019年)

6.中国轻工业联合会科技进步一等奖(2018年，排名第一)

7.第十六届江苏省青年科技奖暨江苏省十大青年科技之星(2018年)

8.江苏省有突出贡献的中青年专家(2018年)

9.江苏省“333”工程人才(2018年)

10.教育部青年人才项目入选者(2016年)

11.江苏省教育工作先进个人(2016年)

12.霍英东教育基金会第十五届高等院校青年教师奖(2016年)

13.酮酸发酵法制备关键技术及产业化-国家技术发明二等奖(2015年，排名第四)

14.江苏省“六大人才高峰”高层次人才支持计划(2015年)

15.江苏省“青蓝工程”优秀青年骨干教师(2014年)

16.国际工业生物过程协会(IFIBiop)优秀青年科学家奖(2014年)

五、国际国内学术组织任职情况

(1) Systems Microbiology and Biomanufacturing执行主编(2019.10-)

(2) Biotechnology and Applied Biochemistry副主编(2021.01-)

(3) Microbial Cell Factories编委(2017.6-)

(4) Amino Acids编委(2021.2-)

(5) Metabolic Engineering Communications编委(2018.10-)

(6) Frontiers in Bioengineering and Biotechnology编委(2015.8-)

(7) Biotechnology Notes编委(2018.11-)

(8) Scientific Reports编委(2015.7-)

(9)《合成生物学》编委(2020.3-)

(10)江苏省教育厅工学3类研究生教指委秘书处负责人(2018.11-)

(11)轻化工助剂化学与技术教育部重点实验室第二届学术委员会委员(2019.7-)

(12)中国生物工程学会食品生物技术专业委员会委员(2019.11-)

(13)中国微生物学会微生物教学工作委员会委员(2016.10-)