A fortuitous collaboration at Rice University has led to the total synthesis of a recently discovered natural antibiotic. The laboratory recreation of a fungus-derived antibiotic, viridicatumtoxin B, may someday help bolster the fight against bacteria that evolve resistance to treatments in hospitals and clinics around the world. As part of the process, Rice organic chemist Dr. K.C. Nicolaou and structural biologist Dr. Yousif Shamoo and their colleagues created and tested a number of variants of viridicatumtoxin B that could lead to the simplified synthesis of a new generation of more effective antibiotics. The work, reported online on August 15, 2014 in the Journal of the American Chemical Society (JACS), focused on a tetracycline discovered in 2008 by scientists who isolated small amounts from penicillium fungi. The yield wasn’t nearly enough for extensive testing, but it provided a basis for the discoverers to analyze its structure through magnetic resonance imaging, Dr. Nicolaou said. “We’re inspired by molecules that are biologically active and have the potential to become medicines one day,” he said. The new discovery belongs to a class of antibiotics known as tetracyclines for their distinctive molecular structure. They proved potent in initial tests on Gram-positive bacteria, so named for a staining technique to mark bacteria that are more susceptible to antibiotics than their Gram-negative counterparts. The first tetracyclines, discovered in the late 1940s, ushered in a new class of powerful antibacterial agents to treat high-mortality diseases, among them anthrax and plague, as well as such bacterial infections as chlamydia, syphilis, and Lyme disease.
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