Fluopsin C was discovered in 1970. It is a broad-spectrum antibiotic that kills a wide range of bacteria and fungi, including strains resistant to other drugs.
Electron paramagnetic resonance
Li’s team at UNC followed the uptake of copper by cultured P. aeruginosa and showed that the copper atoms were incorporated into fluopsin C.
They worked with Lizhi Tao, postdoctoral fellow in Professor David Britt’s lab at the UC Davis Department of Chemistry, using electron paramagnetic resonance, or EPR, to study the synthetic pathway. The researchers found that two small sulfur-containing molecules bind to each copper atom in a mix of cis and trans isomers.
The study shows how Fluopsin C could be synthesized by an enzymatic process instead of using hazardous chemicals. Repurposing copper into an antibiotic in this way is a different response from processes in most organisms, which either sequester or export the metal from the cell, Li said.
EPR is a form of magnetic resonance spectroscopy which is particularly suited to studying metals in organic molecules. Britt’s lab at UC Davis operates the CalEPR center, with seven EPR instruments, the largest facility of its kind on the West coast.
Additional authors on the paper are Jon Patteson, Andrew Putz, William Simke and Henry Bryant III, all at UNC. The work was supported by grants from the NIH and a Packard Fellowship to Li.