A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis
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Author(s)
Zhong, Aoshu
Sun, He G.
Liu, Hung-wen
Rabb, Jennifer
Drennan, Catherine L.
Date Issued
April 2017
Journal
Nature
Publisher
Springer Nature
Citation
Bridwell-Rabb, Jennifer et al. “A B12-Dependent Radical SAM Enzyme Involved in Oxetanocin A Biosynthesis.” Nature 544, 7650 (March 2017): 322–326 © 2017 Macmillan Publishers Limited, part of Springer Nature
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Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1038/NATURE21689
