Department of Chemistry - PhD Student Seminar - NRPSs/PKSs Bioengineering for De Novo Natural Product Biosynthesis

Student: Mr. Zhen HUI

Department: Department of Chemistry, HKUST

Supervisor: Prof. Zhihong GUO

Co-supervisors: Prof. Peiyuan QIAN (OCES), Prof. Xiaoyu TANG (SZBL)

Abstract

Natural products (NPs), characterized by their complex structures and sophisticated modifications, have historically played invaluable roles in drug discovery and development, particuarly in combating infectious and chronic diseases. Among the most prolific NPs, non-ribosomal peptides (NRPSs) and polyketides (PKSs) renowned by remarkable scaffold diversity and structural complexity. Both megaenzymes share a common architectural logic, with minimal module featuring domains responsible for identifying, tethering and incorporating the incoming substrate and elongating intermediate. Additional tailoring domains embedded within modules, alongside free modifying enzymes, further diversify the vast structural repertoire. Leveraging their inherent modular logic and versatile natural recombination, researchers have extensively explored their potential to both derive the known compounds and develop novel structures utilizing the native biosynthetic frameworks. This seminar will give a comprehensive overview of the advancements in NRPSs and PKSs bioengineering, focus on the modular recombination to mimic the natural evolution for the biosynthesis of novel natural compounds. These achievements illuminate pathways toward developing more efficient strategies for novel compounds synthesis, and even design to create novel medicines.