A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis
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 produc...
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| Format: | Article |
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Springer Nature
2018
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| Online Access: | http://hdl.handle.net/1721.1/116346 https://orcid.org/0000-0002-7437-6217 https://orcid.org/0000-0001-5486-2755 |
| _version_ | 1826201740101287936 |
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| author | Zhong, Aoshu Sun, He G. Liu, Hung-wen Rabb, Jennifer Drennan, Catherine L. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Zhong, Aoshu Sun, He G. Liu, Hung-wen Rabb, Jennifer Drennan, Catherine L. |
| author_sort | Zhong, Aoshu |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:56:21Z |
| format | Article |
| id | mit-1721.1/116346 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:56:21Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1163462022-09-27T22:58:34Z A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis Zhong, Aoshu Sun, He G. Liu, Hung-wen Rabb, Jennifer Drennan, Catherine L. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Rabb, Jennifer Drennan, Catherine L. 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. National Institutes of Health (U.S.) (Grant F32-GM108189) 2018-06-15T18:03:53Z 2018-06-15T18:03:53Z 2017-04 2016-07 2018-06-15T17:00:08Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/116346 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 https://orcid.org/0000-0002-7437-6217 https://orcid.org/0000-0001-5486-2755 http://dx.doi.org/10.1038/NATURE21689 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Nature PMC |
| spellingShingle | Zhong, Aoshu Sun, He G. Liu, Hung-wen Rabb, Jennifer Drennan, Catherine L. A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis |
| title | A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis |
| title_full | A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis |
| title_fullStr | A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis |
| title_full_unstemmed | A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis |
| title_short | A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis |
| title_sort | b12 dependent radical sam enzyme involved in oxetanocin a biosynthesis |
| url | http://hdl.handle.net/1721.1/116346 https://orcid.org/0000-0002-7437-6217 https://orcid.org/0000-0001-5486-2755 |
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