Synthesis produces new fungus-derived antibiotic

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 K.C. Nicolaou and structural biologist 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 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.

To find new weapons, especially against "superbugs" that resist nearly all antibiotics, synthetic chemists pursue the complex process of mimicking the structures of effective natural molecules as they build drug candidates atom by atom.

"Tetracyclines are widespread antibiotics today, but bacteria are building resistance to a lot of them," Nicolaou said. "This new tetracycline is not plentiful in nature, so the only way we can make it available to study by biologists for its potential in medicine is to synthesize it in the laboratory."