Knowledge that microbes lead fascinating chemical lives is as old as microbiology itself. Observations in the late 19th century by Burdon-Sanderson (1) that were elaborated on by Pasteur and Joubert (2) gave rise to the idea that compounds secreted by some microbes could have remarkable effects on the lives of others. The accretion of such knowledge continued steadily through the early years of the 20th century until the quantum leap emanating from Fleming’s seminal discovery of penicillin (3). Chain and Florey’s subsequent development of penicillin as a therapeutic agent ushered in not only the golden era of antibiotics but an entire pharmaceutical industry based largely on small-molecule natural products. Since those days, the chemical lives of microbes have been studied largely through labor-intensive and time-consuming approaches that addressed one molecule at a time. Although this time-honored approach has yielded much new knowledge, the rate of discovery slowed down dramatically in recent decades. Perhaps all there was to discover about small-molecule natural products had been discovered. The advent of genomics put a halt to that idea; genomes revealed a great potential diversity of secreted microbial products waiting to be found (4). However, progress in realizing that potential has been slow (5). In PNAS, Watrous et al. offer a brand new way of viewing secreted microbial products that holds great promise in providing the next quantum leap in understanding the fascinating world of microbial chemical ecology (6).
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