The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants
© 2020, The Author(s). Plant halogenated natural products are rare and harbor various interesting bioactivities, yet the biochemical basis for the involved halogenation chemistry is unknown. While a handful of Fe(II)- and 2-oxoglutarate-dependent halogenases (2ODHs) have been found to catalyze regio...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
|
| Online Access: | https://hdl.handle.net/1721.1/134159 |
| _version_ | 1826210937430867968 |
|---|---|
| author | Kim, Colin Y Mitchell, Andrew J Glinkerman, Christopher M Li, Fu-Shuang Pluskal, Tomáš Weng, Jing-Ke |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Kim, Colin Y Mitchell, Andrew J Glinkerman, Christopher M Li, Fu-Shuang Pluskal, Tomáš Weng, Jing-Ke |
| author_sort | Kim, Colin Y |
| collection | MIT |
| description | © 2020, The Author(s). Plant halogenated natural products are rare and harbor various interesting bioactivities, yet the biochemical basis for the involved halogenation chemistry is unknown. While a handful of Fe(II)- and 2-oxoglutarate-dependent halogenases (2ODHs) have been found to catalyze regioselective halogenation of unactivated C–H bonds in bacteria, they remain uncharacterized in the plant kingdom. Here, we report the discovery of dechloroacutumine halogenase (DAH) from Menispermaceae plants known to produce the tetracyclic chloroalkaloid (−)-acutumine. DAH is a 2ODH of plant origin and catalyzes the terminal chlorination step in the biosynthesis of (−)-acutumine. Phylogenetic analyses reveal that DAH evolved independently in Menispermaceae plants and in bacteria, illustrating an exemplary case of parallel evolution in specialized metabolism across domains of life. We show that at the presence of azide anion, DAH also exhibits promiscuous azidation activity against dechloroacutumine. This study opens avenues for expanding plant chemodiversity through halogenation and azidation biochemistry. |
| first_indexed | 2024-09-23T14:57:49Z |
| format | Article |
| id | mit-1721.1/134159 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:57:49Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1341592023-02-24T19:14:19Z The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants Kim, Colin Y Mitchell, Andrew J Glinkerman, Christopher M Li, Fu-Shuang Pluskal, Tomáš Weng, Jing-Ke Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology © 2020, The Author(s). Plant halogenated natural products are rare and harbor various interesting bioactivities, yet the biochemical basis for the involved halogenation chemistry is unknown. While a handful of Fe(II)- and 2-oxoglutarate-dependent halogenases (2ODHs) have been found to catalyze regioselective halogenation of unactivated C–H bonds in bacteria, they remain uncharacterized in the plant kingdom. Here, we report the discovery of dechloroacutumine halogenase (DAH) from Menispermaceae plants known to produce the tetracyclic chloroalkaloid (−)-acutumine. DAH is a 2ODH of plant origin and catalyzes the terminal chlorination step in the biosynthesis of (−)-acutumine. Phylogenetic analyses reveal that DAH evolved independently in Menispermaceae plants and in bacteria, illustrating an exemplary case of parallel evolution in specialized metabolism across domains of life. We show that at the presence of azide anion, DAH also exhibits promiscuous azidation activity against dechloroacutumine. This study opens avenues for expanding plant chemodiversity through halogenation and azidation biochemistry. 2021-10-27T19:58:25Z 2021-10-27T19:58:25Z 2020 2021-08-04T12:33:45Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134159 en 10.1038/S41467-020-15777-W Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Kim, Colin Y Mitchell, Andrew J Glinkerman, Christopher M Li, Fu-Shuang Pluskal, Tomáš Weng, Jing-Ke The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants |
| title | The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants |
| title_full | The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants |
| title_fullStr | The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants |
| title_full_unstemmed | The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants |
| title_short | The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants |
| title_sort | chloroalkaloid acutumine is biosynthesized via a fe ii and 2 oxoglutarate dependent halogenase in menispermaceae plants |
| url | https://hdl.handle.net/1721.1/134159 |
| work_keys_str_mv | AT kimcoliny thechloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT mitchellandrewj thechloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT glinkermanchristopherm thechloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT lifushuang thechloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT pluskaltomas thechloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT wengjingke thechloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT kimcoliny chloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT mitchellandrewj chloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT glinkermanchristopherm chloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT lifushuang chloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT pluskaltomas chloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants AT wengjingke chloroalkaloidacutumineisbiosynthesizedviaafeiiand2oxoglutaratedependenthalogenaseinmenispermaceaeplants |