As a young boy, Southern Methodist University (SMU) researcher Alexander Chase was captivated by the incredible variety of plants in Earth’s tropical rainforests. This early fascination led him to ponder the potential existence of undiscovered species.
Driven by this curiosity, Chase now utilizes a cutting-edge method called Small Molecule In situ Resin Capture (SMIRC) to gather samples from the Earth’s oceans. This innovative technique holds the promise of uncovering compounds that may pave the way for the development of advanced antibiotics.
Microbial natural products stem from microorganisms and form the basis of many vital medicines, particularly antibiotics. Microbes, which are invisible to the naked eye, generate a wide array of chemical compounds throughout their lifecycle, some of which hold significant potential for pharmaceutical use. Traditionally, these compounds are unearthed through a ‘microbe-first’ approach, involving the cultivation of individual strains from wild samples in laboratory settings.
Although this method has proven effective, it has become progressively challenging for researchers to use it to identify new chemical “scaffolds” that underpin the development of chemical compounds. These chemical scaffolds are indispensable for advancing drug discovery.
“Right now, when we collect new samples and culture the microbes, we’re discovering scaffolds that essentially are very similar to the ones we already know about,” explains Chase, an assistant professor in the Roy M. Huffington Department of Earth Sciences. “It’s been really difficult over the last few decades to find something that is new with the ‘microbe-first’ approach, which essentially limits us to the same or similar bacterial strains and their chemical compounds that represent only a fraction of the natural diversity out in the ocean. That’s where SMIRC comes in; it allows us to explore the unknown.”
A recent publication in the journal Nature Communications by Chase and researchers at the University of California San Diego and University of California San Francisco reveals the breakthrough of SMIRC in collecting microbial natural products directly from their natural habitats, eliminating the need for lab cultivation. This innovative approach utilized an absorbent resin, HP-20, which effectively captured the chemicals released by microbes, acting like a sponge.
In a demonstration, the team applied SMIRC in seagrass-covered areas near San Diego and successfully identified an antibiotic compound and chrysoeriol, a plant-based chemical with antibacterial properties, among the collected compounds. Furthermore, a modified SMIRC technique involving the combination of HP-20 with agar resulted in the discovery of aplysiopsene A, reaffirming the effectiveness of SMIRC in recovering valuable compounds.
A recent study utilized the SMIRC technique in a protected marine reserve at Cabrillo National Monument, resulting in the collection of larger samples containing more complex chemical mixtures. The area’s richness in novel compounds remains a mystery, but researchers speculate that minimal human activity in the region may be a contributing factor.
While the newly discovered compounds did not lead to the development of new antibiotics, one compound, known as cabrillostatin, exhibits bioactivity and is now being explored as a potential breakthrough in cancer and heart care.
“The ocean is one of the least explored areas on Earth, especially the deep ocean,” said Chase. “There’s so much we don’t understand about marine microorganisms and the compounds they produce. Because of antibiotic resistance and other health challenges, natural product research is of high priority. With SMIRC, we now have an easily deployable system that makes it possible for researchers to study compounds previously out of reach.”
Journal reference:
- Alexander Bogdanov, Mariam N. Salib, Alexander B. Chase, Heinz Hammerlindl, Mitchell N. Muskat, Stephanie Luedtke, Elany Barbosa da Silva, Anthony J. O’Donoghue, Lani F. Wu, Steven J. Altschuler, Tadeusz F. Molinski & Paul R. Jensen. Small molecule in situ resin capture provides a compound first approach to natural product discovery. Nature Communications, 2024; DOI: 10.1038/s41467-024-49367-x
