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A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis

Author

Listed:
  • Jennifer Bridwell-Rabb

    (Howard Hughes Medical Institute, Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Aoshu Zhong

    (College of Pharmacy, University of Texas
    University of Texas)

  • He G. Sun

    (College of Pharmacy, University of Texas
    University of Texas)

  • Catherine L. Drennan

    (Howard Hughes Medical Institute, Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Hung-wen Liu

    (College of Pharmacy, University of Texas
    University of Texas)

Abstract

Oxetanocin A (OXT-A) is a potent antitumour, antiviral and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne Bacillus megaterium gene cluster that contains four genes: oxsA, oxsB, oxrA and oxrB. Here we show that both the oxsA and oxsB genes are required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, reveals that OXT-A is derived from a 2′-deoxyadenosine phosphate in an OxsB-catalysed ring contraction reaction initiated by hydrogen atom abstraction from C2′. Hence, OxsB represents the first biochemically characterized non-methylating Cbl-dependent AdoMet radical enzyme. X-ray analysis of OxsB reveals the fold of a Cbl-dependent AdoMet radical enzyme, a family of enzymes with an estimated 7,000 members. Overall, this work provides a framework for understanding the interplay of AdoMet and Cbl cofactors and expands the catalytic repertoire of Cbl-dependent AdoMet radical enzymes.

Suggested Citation

  • Jennifer Bridwell-Rabb & Aoshu Zhong & He G. Sun & Catherine L. Drennan & Hung-wen Liu, 2017. "A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis," Nature, Nature, vol. 544(7650), pages 322-326, April.
    • Handle: RePEc:nat:nature:v:544:y:2017:i:7650:d:10.1038_nature21689
    DOI: 10.1038/nature21689
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