Characterization of a Radical Intermediate in Lipoyl Cofactor Biosynthesis

Nicholas D. Lanz, Justin M. Rectenwald, Bo Wang, Elizabeth S. Kakar, Tatiana N. Laremore, Squire J. Booker, Alexey Silakov

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14 Scopus citations


Lipoyl synthase (LipA) catalyzes the final step in the biosynthesis of the lipoyl cofactor, the insertion of two sulfur atoms at C6 and C8 of an n-octanoyl chain. LipA is a member of the radical S-adenosylmethionine (SAM) superfamily of enzymes and uses two [4Fe-4S] clusters to catalyze its transformation. One cluster binds in contact with SAM and donates the requisite electron for the reductive cleavage of SAM to generate two 5′-deoxyadenosyl 5′-radicals, which abstract hydrogen atoms from C6 and C8 of the substrate. By contrast, the second, auxiliary [4Fe-4S] cluster, has been hypothesized to serve as the sulfur donor in the reaction. Such a sacrificial role for an iron-sulfur cluster during catalysis has not been universally accepted. Use of a conjugated 2,4-hexadienoyl-containing substrate analogue has allowed the substrate radical to be trapped and characterized by continuous-wave and pulsed electron paramagnetic resonance methods. Here we report the observation of a 57Fe hyperfine coupling interaction with the paramagnetic signal, which indicates that the iron-sulfur cluster of LipA and its substrate are within bonding distance.

Original languageEnglish (US)
Pages (from-to)13216-13219
Number of pages4
JournalJournal of the American Chemical Society
Issue number41
StatePublished - Oct 21 2015

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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