第542次 SKLBE学术论坛

报告人：波士顿大学 刘平华教授

时间：2021-7-28 (周三) 10:00-11:30

主持人：张立新教授

地点： 实验十八楼315室

【摘要】

According to recent statistics, approximately 60% of drugs marketed between 1940 and 2014 are either natural products or natural product derivatives. In the last decade, technological advances across multiple areas (exponential growth of genomic information, more advanced bioinformatic tools, powerful genetic methods, and affordable gene synthesis) have been integrated to completely re-shape the area of natural product chemistry, which is the focus of Liu’s research. In this talk, I will use some case studies to illustrate the Liu lab approaches to address the following questions:

1.      How to de-replicate to reduce the frequency of re-isolation of known natural products and to increase of our chance of isolating metabolites with low natural abundance;

2.      Mechanistic investigation of novel transformations in the biosynthetic pathways of molecules of interest, with focuses on tailoring enzymes;

3.      Pilot scale production of molecules of interest using synthetic biology approach;

4.      Animal models for identification and evaluation of longevity compounds and their potential applications.

【报告人简介】

刘平华，博士，波士顿大学化学系教授。2001年获得美国明尼苏达大学博士学位，2001-2005年在美国麻省理工学院（MIT）从事博士后研究。2005年至今在波士顿大学依次任助理教授，副教授和教授。刘平华教授研究主要分为三个方向：1）天然产物的生物合成研究； 2)开发长寿化合物及其在开发衰老相关疾病疗法中的应用； 3) 开发合成生物学方法以高产所需化合物。 多年来，致力于研究具有高成药性的碳膦类化合物领域（目前只有 40 种，其中15%具有生物活性），做出主要贡献(Nature, 2005, 437, 838-844; Nature, 2013, 496, 114 - 118)；同时，研究鉴定了长寿化合物麦角硫因，并开发出可工业规模生产的方法（申请美国专利，10167490 B2：刘平华，宋恒，胡文，“通过代谢工程生产麦角硫因（WO 2014100752 A1）”，2013）。在Nature, Angew. Chem. Int. Ed., J. Am. Chem. Soc., Biochemistry等顶级学术刊物上发表多篇重要学术论文。在天然产物生物合成领域取得得了很多有价值的发现。

【报告人代表性论著】

1. Luke J. Higgins, Feng Yan, Pinghua Liu, Hung-wen Liu, Catherine L. Drennan. “Structural Insight into the Biosynthesis of the Antibiotic Fosfomycin by a Mononuclear Iron Enzyme”, Nature, 2005, 437, 838-844.

2. Wei-chen Chang, Mishtu Dey, Pinghua Liu, Steven O. Mansoorabadi, Sung-Ju Moon, Zongbao Zhao, Catherine L. Drennan, and Hung-wen Liu, “An unprecedented 1,2-phosphono migration catalyzed by (S)-2-hydroxypropylphosphonate epoxidase provides evidence for the intermediacy of a cation species in a non-heme mononuclear iron-dependent enzyme-catalyzed reaction”, Nature, 2013, 496, 114 - 118.

3. Luwen Ning^1#, Guan Wang^2#, Zhoufang Li^1#, Wen Hu^{3, 4#}, Qingming Hou², Yin Tong¹, Meng Zhang¹, Li Qin⁴, Xiaoping Chen⁴, Heng-Ye Man^2*, Pinghua Liu^3*, Jiankui He^1* “Quantitative assessment of single-cell sequencing methods using hippocampal neurons”, Sci. Rep., 2015; 5: 11415.

4. Ronghai Cheng,^?1 Lian Wu,^?2 Rui Lai,^?1 Chao Peng,^?3 Nathchar Naowarojna,^?1 Weiyao Hu,^1,4 Xinhao Li,⁴ Stephen A. Whelan,¹ Norman Lee,¹ Juan Lopez,¹ Changming Zhao,^1,5 Youhua Yong,² Jiahui Xue,⁶ Xuefeng Jiang,⁶ Mark W. Grinstaff,^1,7Zixin Deng,⁵ Jiesheng Chen,^4* Qiang Cui,^1* Jiahai Zhou,^2* and Pinghua Liu^1* C-S Bond Formation Using Polysulfide as the Direct Sulfur Source in Anaerobic Ergothioneine Biosynthesis. ACS Catal. (2020), 10, 16, 8981–8994.