(12e) Microbial Biosynthesis of Bioorthogonal Functionalities and Applications

Authors: 
Zhu, X., UC berkeley
Zhang, W., University of California, Berkeley
Research Interests:

Natural products biosynthesized by microbes offer unique functionalities that can be used as chemical handles in bioorthogonal chemistry. Bioorthogonal chemistry have recently emerged as one of the most powerful tools in drug discovery and chemical biology. Despite the importance of the unique chemical functionalities involved in biorthogonal chemistry, the biosynthetic routes to bioorthogonal functionalities are not well understood. In my graduate career, we identified and characterized two biosynthetic pathways in microbes that lead to the generation of a bioorthogonal functionality-terminal alkyne through unprecedented pathways. These pathways were further exploited for tagging various natural products with terminal alkyne functionalities through biochemical pathway engineering. The natural product tagging strategy also enabled the development of an in situ natural products quantification platform based on bioorthogonal chemistry with the newly installed alkyne tag. Using this quantification platform as a screening method, we applied directed evolution strategy to improve the activity of a membrane-bound bifunctional desaturase/acetylenase. This study not only provides alkyne biosynthetic tools that are useful for chemical biology, but it also has applications in which enzymatic generation of terminal alkynes and in situbioorthorgonal chemical transformation are required or preferred.

I would like to continue studying microbial biosynthesis of structurally and functionally interesting chemical functionalities and find applications in chemical biology and drug development.

Teaching Interests:

Aside from my research, I also have teaching experience as a teaching assistant during my graduate life. I led discussion sections, prepared teaching materials and held office hours for a core course â??Kineticsâ? for undergraduate majored in chemical engineering. I also spent two semesters organizing and preparing teaching materials for a seminar-based course â??Berkeley lectures on energy: energy from biomassâ?. I also mentored two graduate students, and two undergraduate students in my group.

Based on my own academic background, I would love to teach general chemical engineering (e.g. Kinetics, Thermodynamics) for undergraduate students. I would also like to develop a course â??Biomolecular Engineeringâ?, which is a combination of lectures and lab sessions. The lectures would focus on the use of chemical engineering principles in the design of biologically-based processes (e.g. microbial fermentation, bioreactors, etc), and also cover topics in biotechnology such as enzyme kinetics, recombinant DNA technology, protein expression, protein engineering, synthetic biology, etc. Students would also have chances to practice basic biotechnical skills in lab sessions, such as molecular cloning, protein purification, enzyme kinetic assays, bioreactor-based fermentation, etc.

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