About 70 percent of the antibiotics
currently in use come from bacteria. Metcalf's fascination with the
ongoing "biological warfare between bacteria" led him to explore the
antimicrobial potential of phosphonates. While phosphonates have
found uses in medicine -- to treat malaria or hypertension
-- this area of research is fairly new, he said.
"No one has even made a dedicated
search for phosphonates in nature," he said.
Metcalf and his collaborators have
analyzed the biological activity of some known phosphonates,such as
the herbicide phosphinothricin. The van der Donk and Zhao groups
have investigated the clinically used phosphonate, fosfomycin.
Kelleher, a biological mass
spectroscopist, has constructed several new, high-resolution Fourier
Transform mass spectrometers, which will help the researchers
isolate previously unknown microbial products that contain the
Nair is an X-ray crystallographer
with expertise in elucidating the three-dimensional structure of
protein and DNA complexes.
The research team has four goals:
the discovery and genetic characterization of phosphonate
biosynthetic pathways; the biochemical reconstruction of those
pathways that have antibiotic or other therapeutic potential; the
bioengineering of medically useful phosphonates and their
biosynthetic enzymes for economical production; and the use of the
latest mass spectrometric technology to discover and engineer
phosphonates and enzymes that contribute to phosphonate metabolism.
"Our role is the discovery of
antibiotics for which there is a critical need and the development
of ways to produce these antibiotics economically," Metcalf said.