BioEd Online

Scientists have succeeded in efficiently mixing and matching the building blocks of a special class of compounds called polyketides inside bacteria. The bioengineering of bacteria in this way could provide doctors with novel antibiotics to treat life-threatening infections.

Over the past few decades, bacteria have evolved to evade the stock of antibiotics we have on hand, leaving doctors with no weapons to fight them. Hospitals have recently seen a dramatic rise in the number of antibiotic-resistant microbes infecting their patients, many of which prove fatal.

To come up with original antibiotics, scientists typically work with the natural chemical defences produced by fungi and bacteria. They attempt to alter these natural antibiotics to produce new ones that can combat illness.

Now researchers have found they might be able to get the bacteria to do this work for them.

Mix and match

Daniel Santi of the Hayward, California-based company Kosan Biosciences and his teammates, investigated one class of compounds produced by bacteria known as polyketides - molecules that contain large rings of carbon and oxygen. Some well-known antibiotics, including erythromycin, are polyketides.

The team picked out bits of DNA known to produce polyketide-making proteins from several different organisms. They then mixed and mached these sections of DNA inside E. coli bacteria.

Santi says that the DNA subunits freely combine inside the E. coli "like lego building blocks". This in turn produces novel conformations of proteins that prompt the formation of new polyketides.

The team improved the ability of the DNA subunits to snap together by adding special sequences to the ends of the genetic fragments, they report in Nature Biotechnology1.

The team has yet to test whether these novel polyketides possess antibiotic properties. But they anticipate that at least some of the compounds produced with this assembly-line approach will be useful.

Santi adds that some natural polyketides have anticancer effects. Perhaps some of the bioengineered E. coli products will have these traits too.

Experts say the approach is welcome in a field that is running dry of ways to make new antibiotics. "The need is obvious and there's been very little in the way of new antibiotics in the past decade," says molecular pharmacologist Jon Clardy of the Harvard Medical School in Boston.