Symbiotic Bacterial Producer of Anti-Cancer Drug ET-743 Identified; Scientists Hope to Grow in Lab without Its Host to Simplify and Speed Up Drug Production

For decades, scientists have known that ET-743, a compound extracted from a marine invertebrate called a mangrove tunicate, can kill cancer cells. The drug has been approved for use in patients in Europe and is currently in clinical trials in the U.S. Scientists suspected that the mangrove tunicate, which is a type of a sea squirt, doesn't actually make ET-743. But the precise origins of the drug, which is also known as trabectedin, were a mystery. By analyzing the genome of the tunicate, along with the microbes that live inside it, using advanced sequencing techniques, researchers at the University of Michigan (U-M) were able to isolate the genetic blueprint of the ET-743's producer--which turns out to be a type of bacteria called Candidatus Endoecteinascidia frumentensis. The findings greatly expand understanding of this microbe and of how ET-743 is produced, the researchers reported online on May 27. 2015 in the journal Environmental Microbiology. They're optimistic that the insights will help make it possible to culture the bacteria in the laboratory without its host. "These symbiotic microbes have long been thought to be the true sources of many of the natural products that have been isolated from invertebrates in the ocean and on the land. But very little is known about them because we're not able to get most of them to grow in a laboratory setting," said study senior author Dr. David Sherman, the Hans W. Vahlteich Professor of Medicinal Chemistry in the College of Pharmacy and a faculty member of the U-M Life Sciences Institute, where his lab is located.
Login Or Register To Read Full Story