Antibiotics made to order

Antimicrobial drug resistance is a global threat to human health. There is an urgent need to discover new antibiotics whose modes of action circumvent prevalent clinical resistance mechanisms. Most antibiotics in clinical use are microbial natural products or their derivatives, whose production is encoded by a biosynthetic gene cluster (BGC) (1). Traditional antibiotic discovery strategies involve screening large microbial strain collections for antibiotic activity, followed by a resource-intensive pursuit of pure material for further characterization. This pipeline is hampered by challenges isolating unexplored microbial taxa and because most BGCs are not expressed during laboratory studies (2, 3). On page 991 of this issue, Wang et al. (4) use in silico discovery of BGCs and chemical synthesis of their predicted products to identify a new lipopeptide that is active against multidrug-resistant (MDR) clinical isolates. Another report by this group also used this approach to identify a promising new antibiotic (5), highlighting its utility.