Microbial Natural Products Discovery and Biosynthesis

Sheng-Xiong Huang

State Key Laboratory of Phytochemistry and Plant Resource in West China, Kunming Institute of Botany, Kunming China

Natural products remain the best sources of drugs and drug leads. Cloning and characterization of natural product biosynthetic machinery from microbes and elucidation of novel enzymes involved in the biosynthesis of natural product will facilitate and set the stage to fully investigate biosynthetic pathway and to biosynthetically engineer new natural product analogues by combinatorial biosynthesis and synthetic biology. In this lecture, I will present two examples to demonstrate the new technology in drug discovery. First, the advanced combinatorial biosynthesis strategies will be introduced to obtain belomycin derivatives with much improved anti-cancer activity, which was recognized as a milestone research achievement, and demonstrated the great potential of synthetic biology in innovative drug discovery. Second, I report that leinamycin biosynthetic intermediate LNM E1 which was isolated from ∆lnmE mutant strain could form a novel DNA-alkylating episulfonium ion to exert its cytotoxicity toward prostate cancer cells under oxidative stress. This application supports the rational for exploring ROS as a mean for targeting cancer cells, and and highlight LNM E1 as a novel lead for the development of anticancer prodrugs activated by ROS.