On December 21, 2022, we were very pleased to invite a young talented expert on Synthetic Biology of Natural Products, Dr. Kenan A. J.Bozhüyük, the project leader from Max Planck Institute for Terrestrial Microbiology, to give us an exciting and inspiring online academic lecture through Tencent meeting. The lecture was chaired by Professor Dr. Xiaofeng Cai. Teachers and graduate students from School of Pharmacy who work in the related area participated in the meeting online.
With the title of "Synthetic Biology of Natural Products: Engineering Enzymatic Assembly Lines to Produce New Bioactive Compounds ", Dr. Bozhüyük shared his recent original research on artificial design and assembly of non-ribosomal peptide synthetase (NRPS) to generate bioactive “unnatural” natural peptides based on theories and techniques of bioinformatics, structural biology and molecular biology. The lecture starts with the mechanism of non-ribosomal peptide (NRP) biosynthesis and the structure of NRPS, then obtains a large number of novelNRPSs through rational splitting and recombination of NRPSs. Followed by screening of potential bioactive peptides using artificial intelligence and high-throughput technology to provide a library of lead compounds for the discovery of new drugs.
The report takes three NRPS engineering technologies invented by Dr. Bozhüyük in recent years as examples to introduce their research work from XU 1.0, eXU2.0 to Synthetic Zipper (SZ) strategy, as well as the differences and advantages and disadvantages between each technology. Then he showed us the principles of these technologies and their application in detail to finally achieve high yields of NRPs with different structures inEscherichia coli. However, at present, these technologies are more mature and efficient in the recombination of NRPSs derived from Gram-negative bacteria with low GC content (40%-50%), and the efficiency is lower in actinomycetes with high GC content (>70%). The related technologies are still in the process of optimization.
At the end of the lecture, Dr. Bozhüyük also briefly introduced Myria Synthetic Biology Company, which was founded based on the NRPS transformation technology he invented. He showed us the general process and ideas of the company's current research on development of new drugs, which gave us a very good example to successfully industrialize laboratory technology.
