Discovery of Unknown Substances and the Quest for Their Value: Marine Natural Products Chemistry

As exemplified by morphine from the poppy and penicillin discovered fromPenicilliummold, certain organisms produce substances with unique structures and effects. Humanity has long utilized these substances for pharmaceuticals and other applications. Against this backdrop, my research focuses on discovering unknown substances from marine organisms in the Nansei Islands and elucidating their value.

The research begins with the collection of organisms that serve as source materials. Specifically, we travel to the coral reefs of Okinawa and Amami Oshima to collect the marine organisms that inhabit them (Fig. 1, left). The types and numbers of organisms inhabiting the tidal flats of the Nansei Islands change drastically depending on the season and location. Therefore, selecting promising samples based on experience is crucial. We are particularly focused on an organism called cyanobacteria, which proliferates from early spring to summer, and are advancing our research on it (Fig. 1, right).

The collected organisms are brought back to the university and soaked in alcohol to extract their constituent components. This crude extract is a mixture of a vast number of substances. Therefore, we proceed with the purification of these components, varying our methods depending on the target of interest. For instance, we advance the purification of components with useful biological activities or novel structures using their ability to inhibit cancer cell proliferation or their ultraviolet light absorption patterns as guides.

Once a pure substance is obtained, the next step is to determine its structure. We collect various data (Fig. 2, left) and piece together the structure, ensuring that all pieces of information are consistent with one another. It is like a "puzzle presented by nature," and arriving at the correct structure requires abandoning all preconceptions and meticulously interpreting the data without compromise to ensure there are no logical inconsistencies. The moment the structure is finally determined, sometimes after months or even years of effort, is a heart-pounding experience filled with a profound sense of accomplishment. In recent years, we have also been utilizing the power of artificial intelligence and high-performance computers to aid in structure determination. Molecules are far too small to be seen directly with the naked eye. However, with modern high-performance computers, we can predict the shape of these invisible molecules with considerable accuracy (Fig. 2, right). By comparing the data predicted by the computer with actual measurement data, we can elucidate the substance's structure.

Once the molecular structure is elucidated, the next step is to investigate its novelty. We use a database containing information on the vast number of substances discovered and synthesized by humanity to date to check whether the same substance has been previously reported. The moment the search result returns "no hits," I am filled with immense joy, knowing that I have become the discoverer of an unknown substance. A "discovery" becomes part of humanity's intellectual heritage when it is published as a paper in a scientific journal. When publishing a precious new substance found after much hardship, it is the discoverer's "parental" instinct to want to send it out into the world with added value. Therefore, we investigate its effects on various organisms, such as its activity against cancer cells, malaria parasites, and COVID-19. Finding value is not easy, but sometimes we uncover remarkable activities. Recently, we issued a press release for a major research achievement reported in 2022 (Fig. 3).

In this way, we conduct research to discover unknown substances from the natural world and to elucidate their structure and value. This is research that creates "1" from zero (i.e., revealing the existence of an unknown substance) and then expands that "1" to "10" or "100" (i.e., discovering the substance's useful value). For chemistry, the discipline that deals with the structure and function of matter, demonstrating the existence of new substances is of fundamental importance. Furthermore, because these are original substances that I myself have discovered, I can pursue the search for their value with strong attachment and patience. Set against the beautiful natural backdrop of the Nansei Islands and their cobalt blue seas, we will continue our quest for unknown substances with groundbreaking value.