Coupling a biosynthetic step with a chemical synthesis step has given a team of chemists at the University of East Anglia, in England, a straightforward way to diversify a single natural product into a family of natural product analogs (J. Am. Chem. Soc., DOI: 10.1021/ja1060406). This so-called chemogenetic approach to modify a natural product could prove useful for increasing the number of antimicrobial and anticancer drug candidates. To test the strategy, Rebecca J. M. Goss and coworkers first introduced a chlorinase gene into Streptomyces coeruleorubidus, a bacterium that produces the uridyl peptide antibiotic pacidamycin. The genetic modification provided the researchers with a selective method for making chloropacidamycin. They then developed a palladium-catalyzed cross-coupling reaction with a boronate ester to install an aryl group in place of the chlorine under mild enough conditions to prevent decomposition of the thermally unstable natural product. Goss and colleagues used the reaction to directly introduce an array of aryl groups to the pacidamycin framework in crude aqueous extracts of the chloropacidamycin fermentation broth.