A fortuitous collaboration 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 work reported this month 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, 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.
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.
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.
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."
Ref : http://pubs.acs.org/doi/abs/10.1021/ja506472u
Synthesis produces new fungus-derived antibiotic
