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Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila

Camptothecin is a chemotherapeutic drug widely used to treat various cancers. Ophiorrhiza pumila is an ideal plant model for the study of camptothecin production, with various advantages for studying camptothecin biosynthesis and regulation. The DNA-binding WRKY transcription factors have a key regu...

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Autores principales: Wang, Can, Hao, Xiaolong, Wang, Yao, Maoz, Itay, Zhou, Wei, Zhou, Zhigang, Kai, Guoyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250654/
https://www.ncbi.nlm.nih.gov/pubmed/35795387
http://dx.doi.org/10.1093/hr/uhac099
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author Wang, Can
Hao, Xiaolong
Wang, Yao
Maoz, Itay
Zhou, Wei
Zhou, Zhigang
Kai, Guoyin
author_facet Wang, Can
Hao, Xiaolong
Wang, Yao
Maoz, Itay
Zhou, Wei
Zhou, Zhigang
Kai, Guoyin
author_sort Wang, Can
collection PubMed
description Camptothecin is a chemotherapeutic drug widely used to treat various cancers. Ophiorrhiza pumila is an ideal plant model for the study of camptothecin production, with various advantages for studying camptothecin biosynthesis and regulation. The DNA-binding WRKY transcription factors have a key regulatory role in secondary metabolite biosynthesis in plants. However, little is currently known about their involvement in camptothecin biosynthesis in O. pumila. We identified 46 OpWRKY genes unevenly distributed on the 11 chromosomes of O. pumila. Phylogenetic and multiple sequence alignment analyses divided the OpWRKY proteins into three subfamilies. Based on spatial expression and co-expression, we targeted the candidate gene OpWRKY6. Overexpression of OpWRKY6 significantly reduced the accumulation of camptothecin compared with the control. Conversely, camptothecin accumulation increased in OpWRKY6 knockout lines. Further biochemical assays showed that OpWRKY6 negatively regulates camptothecin biosynthesis from both the iridoid and shikimate pathways by directly downregulating the gene expression of OpGES, Op10HGO, Op7DLH, and OpTDC. Our data provide direct evidence for the involvement of WRKYs in the regulation of camptothecin biosynthesis and offer valuable information for enriching the production of camptothecin in plant systems.
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spelling pubmed-92506542022-07-05 Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila Wang, Can Hao, Xiaolong Wang, Yao Maoz, Itay Zhou, Wei Zhou, Zhigang Kai, Guoyin Hortic Res Article Camptothecin is a chemotherapeutic drug widely used to treat various cancers. Ophiorrhiza pumila is an ideal plant model for the study of camptothecin production, with various advantages for studying camptothecin biosynthesis and regulation. The DNA-binding WRKY transcription factors have a key regulatory role in secondary metabolite biosynthesis in plants. However, little is currently known about their involvement in camptothecin biosynthesis in O. pumila. We identified 46 OpWRKY genes unevenly distributed on the 11 chromosomes of O. pumila. Phylogenetic and multiple sequence alignment analyses divided the OpWRKY proteins into three subfamilies. Based on spatial expression and co-expression, we targeted the candidate gene OpWRKY6. Overexpression of OpWRKY6 significantly reduced the accumulation of camptothecin compared with the control. Conversely, camptothecin accumulation increased in OpWRKY6 knockout lines. Further biochemical assays showed that OpWRKY6 negatively regulates camptothecin biosynthesis from both the iridoid and shikimate pathways by directly downregulating the gene expression of OpGES, Op10HGO, Op7DLH, and OpTDC. Our data provide direct evidence for the involvement of WRKYs in the regulation of camptothecin biosynthesis and offer valuable information for enriching the production of camptothecin in plant systems. Oxford University Press 2022-04-22 /pmc/articles/PMC9250654/ /pubmed/35795387 http://dx.doi.org/10.1093/hr/uhac099 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nanjing Agricultural University https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Wang, Can
Hao, Xiaolong
Wang, Yao
Maoz, Itay
Zhou, Wei
Zhou, Zhigang
Kai, Guoyin
Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila
title Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila
title_full Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila
title_fullStr Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila
title_full_unstemmed Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila
title_short Identification of WRKY transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in Ophiorrhiza pumila
title_sort identification of wrky transcription factors involved in regulating the biosynthesis of the anti-cancer drug camptothecin in ophiorrhiza pumila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250654/
https://www.ncbi.nlm.nih.gov/pubmed/35795387
http://dx.doi.org/10.1093/hr/uhac099
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