A SURPRISING NUMBER OF blockbuster drugs have sprung from one diverse group of naturally occurring molecules called polyketides, which are produced by soil bacteria and fungi. The list includes the antibiotic erythromycin, a cholesterol-lowering agent called Mevacor, and FK506, a powerful immunosuppressant used on transplant patients.
Scientists would like to custom design more of these molecules, but in most cases, the molecules have proven too complex to synthesize. Now, a team of biochemists and organic chemists at Stanford, Brown, and the University of Wisconsin claims to have solved the problem, using a combination of gene splicing and chemistry. The first results, reported in the latest issue of Science, are several new variants of erythromycin.
According to Stanford team leader Chaitan Khosla, the researchers interrupted the sequence whereby genes in streptomyces bacteria produce the antibiotic. They then added man-made chemicals to the mutated cells. These are incorporated into the new versions of erythromycin. Khosla and his colleagues have started Kosan Biosciences Inc. in Burlingame, Calif., where they hope to design thousands of polyketides targeted at heart disease, cancer, and drug resistant bugs.