Direct dimerization simplifies the synthesis of himastatin and elucidates its mode of action

_W ^{ith tant} rent _{need modes urgent}^{the bacteria} frontline _{for (of 1}^emergence_{). One antibiotics action}^that_emerging therapeutics, _is^{can of}_increasingly^{drug-resis- evade}_{with strategy new}^cur- the to address this need is to revisit previously identified antibiotics of promise and apply modern medicinal chemistry and biochemical tools to improve their activity and unveil their often ill-defined modes of action (2, 3). Among such natural products is himastatin (1), a dimeric peptide antibiotic isolated in 1990 that shows good activity against Gram-positive bacteria, albeit through a largely unknown mode of action (4). On page 894 of this issue, D’Angelo et al. (5) develop an efficient chemical synthesis of himastatin through a bioinspired dimerization of its native monomeric units. This approach provides a blueprint to access not only this complex target and its derivatives, but also molecular probes that allow for its mode of action to be elucidated (5).