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An activity-resistance trade-off constrains enzyme evolution

Alexander W Sarkis1, Jens Laurids Sørensen2, Teis Esben Sondergaard2

  • 1Graduate Program in Biochemistry and Biophysics, Department of Biochemistry, Brandeis University, Waltham, MA 02453.

Proceedings of the National Academy of Sciences of the United States of America
|July 23, 2026
PubMed
Summary

Fungal self-resistance to mycophenolic acid (MPA) evolved alongside a trade-off between enzyme activity and resistance. Pre-existing resistance to ribavirin-5'-monophosphate (RVP) may have paved the way for MPA biosynthesis.

Keywords:
IMP dehydrogenasebiosynthetic gene clusterdrug resistanceenzyme evolutionmycophenolic acid

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