Revitalizing microbial secondary metabolites in drug discovery: current challenges and emerging solutions

Abstract

Microbial secondary metabolites are compounds that exhibit diverse biological activities, including antibiotic and immunosuppressive activities. Compared with synthetic compounds, they contain more asymmetric carbon atoms and exhibit greater chemical structural diversity, making them an important source for the discovery of pharmaceuticals and agrochemicals. However, in recent drug-discovery efforts, the robot-assisted high-throughput screening of large numbers of samples has become mainstream. Moreover, combinatorial compound libraries have increasingly served as the primary source of drug discovery, replacing microbial metabolites, which remain labor-intensive to isolate. However, advances in informatics and biotechnology are helping to overcome the traditional limitations of microbial metabolites, such as repeated compound isolation and low productivity. This review considers key challenges in microbial screening and introduces recent attempts to overcome them.