Compounds produced naturally by living things have long been a mainstay of drug research and fields such as ecology and chemical biology. Concerns that researchers may not be able to sustain the natural product discovery pipeline have motivated a comprehensive analysis of the history and current status of the field and a prediction of its future prospects.
William H. Gerwick of the University of California, San Diego, Roger G. Linington of Simon Fraser University, and coworkers studied 52,000 microbial and marine-based natural products discovered between 1941 and 2015 (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1614680114). Their analysis led them to conclude that reports of the death of natural product discovery are greatly exaggerated. “The development of innovative discovery methods will continue to yield compounds with unique structural and biological properties,” they predict.
The study reveals that the number of natural products discovered each year was low in the early 1940s and then grew substantially, possibly owing to growth in the number of practitioners and improved scientific instrumentation. The number has plateaued since the 1990s. Over the total time span, structurally unique compounds have represented a decreasing percentage of the total number of compounds isolated.
The researchers note that exploring new marine and microbial species tends to promote the discovery of novel structures. They also found that although the possible universe of natural product structures is high, the number of compounds discovered in each chemical class has been low, suggesting that natural selection pressures limit the scope of structural diversity. However, they believe significant opportunities remain for finding novel compounds in a range of sources and with different discovery methods.