Bioactive fluorinated compounds are highly desired as pharmaceuticals and agrochemicals. But the very properties of fluorine that allow it to enhance the desired reactivities of these classes of compounds also make it difficult to work with synthetically. And only one organofluorine biosynthetic pathway is known: the fluoroacetate pathway in the soil bacterium Streptomyces cattleya. A team led by Michelle C. Y. Chang of the University of California, Berkeley, has now identified other biosynthetic pathways that can incorporate fluorine into polyketides, a broad class of natural products with antibiotic, antiparasitic, insecticidal, and other functions (Science 2013, DOI: 10.1126/science.1242345). Although the enzymes normally don’t process fluorinated compounds, they have enough substrate flexibility to do so. Working both in vitro and in vivo with engineered Escherichia coli, Chang and colleagues used enzymes from polyketide synthase systems to go from fluoroacetate to polyketide lactones with fluorine site-selectively incorporated into the polyketide backbone.