Over 300 new macrolide compounds were synthesized by a team of scientists in the Myers lab at Harvard. Macrolides are a class of organic compounds with antibiotic properties that are used to treat a wide variety of infections, from pneumonia to chlamydia. Over time however, bacteria develop resistances to currently prescribed antibiotics, so scientists must continue to create new compounds to treat infections. The compounds created in this study will be further tested for their use as prescription antibiotics.

One macrolide compound called erythromycin is produced naturally by a bacterium that lives in soils. Traditionally, it is harvested from the bacteria and given to patients to treat infections. For decades chemists have made variations of erythromycin, as well as other antibiotics, in a process called semi-synthesis. Starting from erythromycin, they add or remove groups of atoms to make a closely related molecule. Some of these variations can even be effective against bacteria that have developed a resistance to erythromycin.

Rather than starting with a naturally-derived macrolide compound like erythromycin, Myers and his team started from scratch. In the experiment, they made (or purchased) eight simple starting components and then combined them to achieve a final compound. This approach, called convergent synthesis, allows many more types of compounds to be made, by beginning with small variants of the starting components or adding variations to the synthesis along the way. They made over 300 variations. While erythromycin had been in the laboratory in 1981, the application of convergent synthesis to a whole class of complex molecules like macrolides is revolutionary. Building the molecule from the ground up gives synthetic chemists much more control over the shape and chemical groups of the final compound. The Myers team applied the tools of modern chemistry to make exponentially more types of antibiotics than was previously possible and is now testing them for their medicinal use.


Acknowledgements:
Thank you to Christopher Gerry, a graduate student in the Department of Chemistry and Chemical Biology at Harvard, for sharing his insight on the topic.

Original Article:
A platform for the discovery of new macrolide antibiotics, Nature

Media Coverage:
Hundreds of antibiotics built from scratch, Nature News
Antibiotics from scratch, The Scientist

Managing Correspondent: Anna Waldeck

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