Abstract
The biosynthesis of the natural product oxetanocin has been connected to a plasmid‐borne Bacillus megaterium gene cluster that contains two genes involved in oxetanocin production (oxsA and oxsB). Here, we present detailed structural and biochemical analysis that confirms the involvement of the cobalamin (Cbl) dependent S□adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD‐domain phosphohydrolase enzyme, OxsA, in oxetanocin production. These studies of OxsB provide a framework for understanding the coordination of AdoMet and Cbl in performing chemistry and reveal an HD‐domain phosphohydrolase enzyme with a restructured active site specific for a phosphorylated oxetanocin compound. Our crystallographic endeavors have allowed for elucidation of a biochemical scheme for the production of oxetanocin, expanded the catalytic repertoire of the HD‐domain phosphohydrolase enzyme superfamily, and provided the first structure of a Cbl‐dependent AdoMet radical enzyme.Support or Funding InformationSupport for this work came from National Institute of Health Grants F32‐GM108189 (J.B.‐R.) and GM035906 (H.‐w.L.), and the Welch Foundation grant F‐1511 (H.‐w.L.). C.L.D. is a Howard Hughes Medical Institute Investigator. This work is also based upon research conducted at the Northeastern Collaborative Access Team beamlines, which are funded by the National Institute of General Medical Sciences from the National Institutes of Health (P41 GM103403). The Pilatus 6M detector on 24‐ID‐C beam line is funded by a NIH‐ORIP HEI grant (S10 RR029205). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE‐AC02‐06CH11357.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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