Molecular insights into a distinct class of terpenoid cyclases
Abstract Terpenoid cyclases (TCs) account for the synthesis of the most widespread and diverse natural compounds. A sesquiterpene cyclase termed BcABA3 from an abscisic acid-producing fungus Botrytis cinerea that yields (2Z,4E)-α-ionylideneethane but lacks signature feature of canonical TCs represen...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55717-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559250442125312 |
|---|---|
| author | Siyu Li Jian-Wen Huang Jian Min Hao Li Meidan Ning Shuyu Zhou Yu Yang Chun-Chi Chen Rey-Ting Guo |
| author_facet | Siyu Li Jian-Wen Huang Jian Min Hao Li Meidan Ning Shuyu Zhou Yu Yang Chun-Chi Chen Rey-Ting Guo |
| author_sort | Siyu Li |
| collection | DOAJ |
| description | Abstract Terpenoid cyclases (TCs) account for the synthesis of the most widespread and diverse natural compounds. A sesquiterpene cyclase termed BcABA3 from an abscisic acid-producing fungus Botrytis cinerea that yields (2Z,4E)-α-ionylideneethane but lacks signature feature of canonical TCs represents a distinct type of TCs. Here, we report the crystal structures of BcABA3, a closely related RuABA3 from Rutstroemia sp. and a bacterial SkABA3 from Shimazuella kribbensis. These ABA3 proteins adopt an all-α-helix fold and bind pyrophosphate moiety of farnesyl pyrophosphate by Glu-chelated Mg2+ ion cluster. We conduct mutagenesis experiments to validate the role of the substrate-binding residues. SkABA3 appears to yield compounds that are distinct from (2Z,4E)-α-ionylideneethane. These results not only provide the molecular insight into ABA3 proteins that serve as an important basis to the future investigation of this class of TCs, but also reveal the existence of more uncharacterized terpenoids synthesized via dedicated machineries. |
| format | Article |
| id | doaj-art-e441544e97ce44a88f195c5efb5f6489 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e441544e97ce44a88f195c5efb5f64892025-01-05T12:40:04ZengNature PortfolioNature Communications2041-17232025-01-011611810.1038/s41467-024-55717-6Molecular insights into a distinct class of terpenoid cyclasesSiyu Li0Jian-Wen Huang1Jian Min2Hao Li3Meidan Ning4Shuyu Zhou5Yu Yang6Chun-Chi Chen7Rey-Ting Guo8State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Hongshan Laboratory, School of Life Sciences, Hubei UniversityAbstract Terpenoid cyclases (TCs) account for the synthesis of the most widespread and diverse natural compounds. A sesquiterpene cyclase termed BcABA3 from an abscisic acid-producing fungus Botrytis cinerea that yields (2Z,4E)-α-ionylideneethane but lacks signature feature of canonical TCs represents a distinct type of TCs. Here, we report the crystal structures of BcABA3, a closely related RuABA3 from Rutstroemia sp. and a bacterial SkABA3 from Shimazuella kribbensis. These ABA3 proteins adopt an all-α-helix fold and bind pyrophosphate moiety of farnesyl pyrophosphate by Glu-chelated Mg2+ ion cluster. We conduct mutagenesis experiments to validate the role of the substrate-binding residues. SkABA3 appears to yield compounds that are distinct from (2Z,4E)-α-ionylideneethane. These results not only provide the molecular insight into ABA3 proteins that serve as an important basis to the future investigation of this class of TCs, but also reveal the existence of more uncharacterized terpenoids synthesized via dedicated machineries.https://doi.org/10.1038/s41467-024-55717-6 |
| spellingShingle | Siyu Li Jian-Wen Huang Jian Min Hao Li Meidan Ning Shuyu Zhou Yu Yang Chun-Chi Chen Rey-Ting Guo Molecular insights into a distinct class of terpenoid cyclases Nature Communications |
| title | Molecular insights into a distinct class of terpenoid cyclases |
| title_full | Molecular insights into a distinct class of terpenoid cyclases |
| title_fullStr | Molecular insights into a distinct class of terpenoid cyclases |
| title_full_unstemmed | Molecular insights into a distinct class of terpenoid cyclases |
| title_short | Molecular insights into a distinct class of terpenoid cyclases |
| title_sort | molecular insights into a distinct class of terpenoid cyclases |
| url | https://doi.org/10.1038/s41467-024-55717-6 |
| work_keys_str_mv | AT siyuli molecularinsightsintoadistinctclassofterpenoidcyclases AT jianwenhuang molecularinsightsintoadistinctclassofterpenoidcyclases AT jianmin molecularinsightsintoadistinctclassofterpenoidcyclases AT haoli molecularinsightsintoadistinctclassofterpenoidcyclases AT meidanning molecularinsightsintoadistinctclassofterpenoidcyclases AT shuyuzhou molecularinsightsintoadistinctclassofterpenoidcyclases AT yuyang molecularinsightsintoadistinctclassofterpenoidcyclases AT chunchichen molecularinsightsintoadistinctclassofterpenoidcyclases AT reytingguo molecularinsightsintoadistinctclassofterpenoidcyclases |