Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila
Abstract Background The anticancer drug camptothecin (CPT), first isolated from Camptotheca acuminata, was subsequently discovered in unrelated plants, including Ophiorrhiza pumila. Unlike known monoterpene indole alkaloids, CPT in C. acuminata is biosynthesized via the key intermediate strictosidin...
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doaj-c4a98c4f4e9b4852a145d7d4ad86f8db2021-06-20T11:29:51ZengBMCBMC Biology1741-70072021-06-0119111610.1186/s12915-021-01051-yDivergent camptothecin biosynthetic pathway in Ophiorrhiza pumilaMengquan Yang0Qiang Wang1Yining Liu2Xiaolong Hao3Can Wang4Yuchen Liang5Jianbo Chen6Youli Xiao7Guoyin Kai8CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Core Facility Centre, Institute of Plant Physiology and Ecology, Chinese Academy of SciencesLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical UniversityCAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Core Facility Centre, Institute of Plant Physiology and Ecology, Chinese Academy of SciencesLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical UniversityLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical UniversityCAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Core Facility Centre, Institute of Plant Physiology and Ecology, Chinese Academy of SciencesInstitute of Plant Biotechnology, School of Life Sciences, Shanghai Normal UniversityCAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Core Facility Centre, Institute of Plant Physiology and Ecology, Chinese Academy of SciencesLaboratory of Medicinal Plant Biotechnology, College of Pharmacy, Zhejiang Chinese Medical UniversityAbstract Background The anticancer drug camptothecin (CPT), first isolated from Camptotheca acuminata, was subsequently discovered in unrelated plants, including Ophiorrhiza pumila. Unlike known monoterpene indole alkaloids, CPT in C. acuminata is biosynthesized via the key intermediate strictosidinic acid, but how O. pumila synthesizes CPT has not been determined. Results In this study, we used nontargeted metabolite profiling to show that 3α-(S)-strictosidine and 3-(S), 21-(S)-strictosidinic acid coexist in O. pumila. After identifying the enzymes OpLAMT, OpSLS, and OpSTR as participants in CPT biosynthesis, we compared these enzymes to their homologues from two other representative CPT-producing plants, C. acuminata and Nothapodytes nimmoniana, to elucidate their phylogenetic relationship. Finally, using labelled intermediates to resolve the CPT biosynthesis pathway in O. pumila, we showed that 3α-(S)-strictosidine, not 3-(S), 21-(S)-strictosidinic acid, is the exclusive intermediate in CPT biosynthesis. Conclusions In our study, we found that O. pumila, another representative CPT-producing plant, exhibits metabolite diversity in its central intermediates consisting of both 3-(S), 21-(S)-strictosidinic acid and 3α-(S)-strictosidine and utilizes 3α-(S)-strictosidine as the exclusive intermediate in the CPT biosynthetic pathway, which differs from C. acuminata. Our results show that enzymes likely to be involved in CPT biosynthesis in O. pumila, C. acuminata, and N. nimmoniana have evolved divergently. Overall, our new data regarding CPT biosynthesis in O. pumila suggest evolutionary divergence in CPT-producing plants. These results shed new light on CPT biosynthesis and pave the way towards its industrial production through enzymatic or metabolic engineering approaches.https://doi.org/10.1186/s12915-021-01051-yBiosynthesisCamptothecinIn vivo labellingOphiorrhiza pumilaStrictosidine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mengquan Yang Qiang Wang Yining Liu Xiaolong Hao Can Wang Yuchen Liang Jianbo Chen Youli Xiao Guoyin Kai |
spellingShingle |
Mengquan Yang Qiang Wang Yining Liu Xiaolong Hao Can Wang Yuchen Liang Jianbo Chen Youli Xiao Guoyin Kai Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila BMC Biology Biosynthesis Camptothecin In vivo labelling Ophiorrhiza pumila Strictosidine |
author_facet |
Mengquan Yang Qiang Wang Yining Liu Xiaolong Hao Can Wang Yuchen Liang Jianbo Chen Youli Xiao Guoyin Kai |
author_sort |
Mengquan Yang |
title |
Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila |
title_short |
Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila |
title_full |
Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila |
title_fullStr |
Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila |
title_full_unstemmed |
Divergent camptothecin biosynthetic pathway in Ophiorrhiza pumila |
title_sort |
divergent camptothecin biosynthetic pathway in ophiorrhiza pumila |
publisher |
BMC |
series |
BMC Biology |
issn |
1741-7007 |
publishDate |
2021-06-01 |
description |
Abstract Background The anticancer drug camptothecin (CPT), first isolated from Camptotheca acuminata, was subsequently discovered in unrelated plants, including Ophiorrhiza pumila. Unlike known monoterpene indole alkaloids, CPT in C. acuminata is biosynthesized via the key intermediate strictosidinic acid, but how O. pumila synthesizes CPT has not been determined. Results In this study, we used nontargeted metabolite profiling to show that 3α-(S)-strictosidine and 3-(S), 21-(S)-strictosidinic acid coexist in O. pumila. After identifying the enzymes OpLAMT, OpSLS, and OpSTR as participants in CPT biosynthesis, we compared these enzymes to their homologues from two other representative CPT-producing plants, C. acuminata and Nothapodytes nimmoniana, to elucidate their phylogenetic relationship. Finally, using labelled intermediates to resolve the CPT biosynthesis pathway in O. pumila, we showed that 3α-(S)-strictosidine, not 3-(S), 21-(S)-strictosidinic acid, is the exclusive intermediate in CPT biosynthesis. Conclusions In our study, we found that O. pumila, another representative CPT-producing plant, exhibits metabolite diversity in its central intermediates consisting of both 3-(S), 21-(S)-strictosidinic acid and 3α-(S)-strictosidine and utilizes 3α-(S)-strictosidine as the exclusive intermediate in the CPT biosynthetic pathway, which differs from C. acuminata. Our results show that enzymes likely to be involved in CPT biosynthesis in O. pumila, C. acuminata, and N. nimmoniana have evolved divergently. Overall, our new data regarding CPT biosynthesis in O. pumila suggest evolutionary divergence in CPT-producing plants. These results shed new light on CPT biosynthesis and pave the way towards its industrial production through enzymatic or metabolic engineering approaches. |
topic |
Biosynthesis Camptothecin In vivo labelling Ophiorrhiza pumila Strictosidine |
url |
https://doi.org/10.1186/s12915-021-01051-y |
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