Novel Natural Products Open the Door of Chemical Biology and Medicinal Chemistry

Exploitation of novel small molecules from natural sources such as microbial metabolites, medicinal plants, and marine invertebrates has contributed to the discovery of lead molecules for drugs as well as research tools on chemical biology. Chemical biology based on forward/reverse chemical genetics is a new paradigm that accelerates drug development and the functional analysis of genes and proteins. Moreover, novel natural products with unique structural or biological characteristics attract both chemists and biologists, thereby developing the field of chemical biology and medicinal chemistry. We have discovered several novel bioactive microbial metabolites by both in vivo cell–based phenotypic screenings and in vitro target–oriented screenings, and investigated their modes of action using a chemical genetics or a chemical genomics approach. In this review, we focus on the following topics; i) recent screening technology and the chemical library, ii) overview of bioactive natural products and semi–synthetic derivatives we have discovered, iii) chemical genetics approach for apoptosis signaling pathway, iv) chemical genomics approach for target identification of antifungal agent, and v) perspective.