Chemists developed a new way to synthesize himastatin, a natural compound that has shown potential as an antibiotic. A new strategy for producing a natural compound could also be used to generate variants with even stronger antimicrobial activity.

Using their new synthesis, the researchers were able not only to produce himastatin but also to generate variants of the molecule, some of which also showed antimicrobial activity. They also discovered that the compound appears to kill bacteria by disrupting their cell membranes. The researchers now hope to design other molecules that could have even stronger antibiotic activity.

«What we want to do right now is learn the molecular details about how it works, so we can design structural motifs that could better support that mechanism of action. A lot of our effort right now is to learn more about the physicochemical properties of this molecule and how it interacts with the membrane,» says Mohammad Movassaghi, an MIT professor of chemistry and one of the senior authors of the study.

Brad Pentelute, an MIT professor of chemistry, is also a senior author of the study, which appears today in Science. MIT graduate student Kyan D’Angelo is the lead author of the study, and graduate student Carly Schissel is also an author.

Mimicking nature

Himastatin, which is produced by a species of soil bacteria, was first discovered in the 1990s. In animal studies, it was found to have anticancer activity, but the required doses had toxic side effects. The compound also showed potential antimicrobial activity, but that potential hasn’t been explored in detail, Movassaghi says.

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Materials provided by Massachusetts Institute of Technology. Original written by Anne Trafton. Note: Content may be edited for style and length.