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Modular synthesis enables molecular ju-jitsu in the fight against antibiotic resistance

An ancient resistance mechanism poses a problem when using streptogramin antibiotics. A modular approach to drug synthesis exploits this same mechanism to generate an antibiotic that avoids the emergence of resistance.
  1. Daniel J. Blair

    1. Daniel J. Blair is in the Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

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  2. Martin D. Burke

    1. Martin D. Burke is in the Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

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The development of resistance to antibiotics by microorganisms is a problem that has been billions of years in the making, but we don’t have as long as that to solve it1,2. One way to speed up the search for solutions is to harness human creativity and modern science to rationally design resistance-evasive variants of naturally occurring antibiotic molecules3,4. Unfortunately, such molecules often have to be synthesized from scratch using long, highly customized sequences of reactions that are prohibitively slow and impractical at large scales. Writing in Nature, Li et al.5 report how a modular synthesis of the structurally complex antibacterial compound virginiamycin M2 (VM2), based on easily interchangeable molecular building blocks, has provided access to VM2 derivatives that could not previously have been prepared — and has thereby enabled the rational development of a variant that evades an ancient resistance mechanism.

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Nature 586, 32-33 (2020)

doi: https://doi.org/10.1038/d41586-020-02565-1

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