Evolutionary adaptations that enable enzymes to tolerate oxidative stress

James A. Imlay, Ramakrishnan Sethu, Sanjay Kumar Rohaun

Research output: Contribution to journalReview articlepeer-review


Biochemical mechanisms emerged and were integrated into the metabolic plan of cellular life long before molecular oxygen accumulated in the biosphere. When oxygen levels finaly rose, they threatened specific types of enzymes: those that use organic radicals as catalysts, and those that depend upon iron centers. Nature has found ways to ensure that such enzymes are still used by contemporary organisms. In some cases they are restricted to microbes that reside in anoxic habitats, but in others they manage to function inside aerobic cells. In the latter case, it is frequently true that the ancestral enzyme has been modified to fend off poisoning. In this review we survey a range of protein adaptations that permit radical-based and low-potential iron chemistry to succeed in oxic environments. In many cases, accessory domains shield the vulnerable radical or metal center from oxygen. In others, the structures of iron cofactors evolved to less oxidizable forms, or alternative metals replaced iron altogether. The overarching view is that some classes of biochemical mechanism are intrinsically incompatible with the presence of oxygen. The structural modification of target enzymes is an under-recognized response to this problem.

Original languageEnglish (US)
Pages (from-to)4-13
Number of pages10
JournalFree Radical Biology and Medicine
StatePublished - Aug 20 2019


  • Hydrogen peroxide
  • Iron-sulfur clusters
  • Obligate anaerobiosis
  • Radical enzymes
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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