Seminar by scientists from Shanghai Jiaotong University
10:00~10:20 Prof. Yan Feng:
A short video about Shanghai Jiao Tong University and Introduction to its Department of Biology
10:20~11:10 Prof. Zixin Deng1:
Expanding the Metabolic Power of the Mined NPs Pathways
11:10~12:00 Prof. Yan Feng2:
Enzyme molecular evolution in synthetic biology: a key role from proof-of-concept towards precision function
Everyone is welcome
1) Expanding the Metabolic Power of the Mined NPs Pathways
Zixin Deng, Distinguished professor
State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University
800 Dongchuan Road, Minhang District, Shanghai, R. China
E-mail: zxdeng@sjtu.edu.cn
In this talk, I will discuss the future directions towards the discovery and development of novel antibiotics NPs by pathway engineering, combinatorial biosynthesis and synthetic biology. Two classes of antibiotics will be the central theme for my presentation. First is an old class of aminoglycosides (AGs) drugs, which remains a valuable component of the antibiotic arsenal, despite their inherent toxicity and the global spread of bacterial resistance. Recent studies have continued to reveal the fascinating biochemistry of AG biosynthesis and the rich potential in their pathway engineering. In particular, parallel pathways have been shown to be common and widespread in AG biosynthesis, highlighting nature's ingenuity in accessing diverse natural products from a limited set of genes.
A second extensively investigated group of NPs is the structurally-related peptidyl nucleoside antibiotics. Their mechanistic insights representing very distinctive enzymatic reactions involved in the biosynthesis of their building blocks, nucleoside skeleton and peptidyl moieties were successfully used for the engineering of the industrial polyoxin producer as efficient cell factories for components optimization and successful production of the hybrid nucleoside antibiotics. As successful examples, introducing heterologous genes from one nucleoside antibiotics nikkomycin producer into an industrial polyoxin producer generated seven polyoxin-nikkomycin designer hybrid antibiotics (designated as nikkoxin A-G), some of which were significantly more potent against indicator human or plant fungal pathogens than both parental antibiotics.
Apparently, elucidation of the molecular mechanisms for aminoglycosides as well as for different nucleoside antibiotics biosynthesis would greatly expand the ways for rational designing and generation of natural artificial molecules with enhanced/selective bioactivity.
2) Enzyme molecular evolution in synthetic biology: a key role from proof-of-concept towards precision function
Yan Feng, Distinguished professor
Shanghai Jiao Tong University
800 Dongchuan Road, Minhang District, Shanghai, R. China
E-mail: yfeng2009@sjtu.edu.cn
Synthetic biology plays an important role in not only revealing the complicated functions of organisms but also providing a promising route for bio‐manufactures. In past years, many successful cases are reported to demonstrate the proof‐of‐concept of synthetic biology. However, we still faced the challenges for building a cost‐efficient process due to shortages of suitable enzymes for the desired reactions. Therefore, more and more attentions focus on molecular evolution of enzymes based on the knowledge of enzyme catalytic mechanisms. Here, we give some examples for discovering and generating the novel functional enzymes and exploring their uses in artificial synthetic pathways. The precise control of catalytic units will greatly enhance the ability to control the biological system. The trend from a simple copy and transfer of heterologous gene to fine tuning of the enzyme functions and directed adaption will provide a new path for targeting the precision function in synthetic biology.
Representative Publications:
- Zhuang Y, Yang GY, Chen XH, Liu Q, Zhang XL, Deng ZX, Feng Y*. Biosynthesis of plant-derived ginsenoside Rh2 in yeast via repurposing a key promiscuous microbial enzyme. Metab Eng, 2017, 42: 25-32.
- Cui L, Zhu Y, Guan XQ, Deng ZX, Bai LQ*, Feng Y*. De novo biosynthesis of beta-valienamine in engineered Streptomyces hygroscopicus 5008. ACS Synth Biol, 2016, 5(1): 15-20.
- Hoque#, Zhang Y#, Chen LQ, Yang GY, Khatun MA, Chen HF, Hao L, Feng Y*, Stepwise loop insertion strategy for active site remodeling to generate novel enzyme functions, ACS Chem Biol, 2017, 15(5):1188‐1193