Development of Atropa belladonna L. Plants with High-Yield Hyoscyamine and without Its Derivatives Using the CRISPR/Cas9 System

Zeng, Lingfeng; Zhang, Qiaozhuo; Jiang, Chunxue; Zheng, Yi-Nan; Zuo, Youwei; Qin, Jianbo; Liao, Zhihua; Hongping, Deng

doi:10.3390/ijms22041731

Cited by 32 publications

(12 citation statements)

References 36 publications

(55 reference statements)

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“…Due to the fact that 2-ODDs were involved in the biosynthesis of various phytochemicals, including glucosinolates, flavonoids, and alkaloids [ 34 , 35 ]. In particular, NR (NCBI non-redundant protein sequences) described transcript 49,882 as hyoscyamine 6-dioxygenase, which catalyzed the epoxidation of scopolamine at the C6 position [ 36 ]. They may also play an important role in DA biosynthesis.…”

Section: Resultsmentioning

confidence: 99%

Integrating Metabolomics and Transcriptomics to Unveil Atisine Biosynthesis in Aconitum gymnandrum Maxim

Chen

Tian

Jin

et al. 2022

IJMS

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Diterpene alkaloids (DAs) are characteristic compounds in Aconitum, which are classified into four skeletal types: C18, C19, C20, and bisditerpenoid alkaloids. C20-DAs are thought to be the precursor of the other types. Their biosynthetic pathway, however, is largely unclear. Herein, we combine metabolomics and transcriptomics to unveil the methyl jasmonate (MJ) inducible biosynthesis of DAs in the sterile seedling of A. gymnandrum, the only species in the Subgenus Gymnaconitum (Stapf) Rapaics. Target metabolomics based on root and aerial portions identified 51 C19-DAs and 15 C20-DAs, with 40 inducible compounds. The highest content of C20-DA atisine was selected for further network analysis. PacBio Isoform sequencing integrated with RNA sequencing not only provided the full-length transcriptome but also their response to induction, revealing 1994 genes that exhibited up-regulated expression. Further, 38 genes involved in terpenoid biosynthesis were identified, including 7 diterpene synthases. In addition to the expected function of the four diterpene synthases, AgCPS5 was identified to be a new ent-8,13-CPP synthase in Aconitum and could also combine with AgKSL1 to form the C20-DAs precursor ent-atiserene. Combined with multiple network analyses, six CYP450 and seven 2-ODD genes predicted to be involved in the biosynthesis of atisine were also identified. This study not only sheds light on diterpene synthase evolution in Aconitum but also provides a rich dataset of full-length transcriptomes, systemic metabolomes, and gene expression profiles, setting the groundwork for further investigation of the C20-DAs biosynthesis pathway.

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Section: Resultsmentioning

confidence: 99%

Integrating Metabolomics and Transcriptomics to Unveil Atisine Biosynthesis in Aconitum gymnandrum Maxim

Chen

Tian

Jin

et al. 2022

IJMS

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“…Atropa belladonna produces a small amount of hyoscyamine and its structural analogs, anisodamine, and scopolamine. Zeng et al. (2021) used CRISPR/Cas9 to disrupt hyoscyamine 6β-hydroxylase (AbH6H).…”

Section: Heterologous Expression Of Secondary Metabolites In Plantsmentioning

confidence: 99%

“…(2021) used CRISPR/Cas9 to disrupt hyoscyamine 6β-hydroxylase (AbH6H). The transgenic plants produced a significantly higher hyoscyamine content but without anisodamine and scopolamine alkaloids ( Zeng et al., 2021 ). In another study, Karlson et al.…”

Section: Heterologous Expression Of Secondary Metabolites In Plantsmentioning

confidence: 99%

Plant-based expression platforms to produce high-value metabolites and proteins

Kulshreshtha¹,

Sharma

Padilla³

et al. 2022

Front. Plant Sci.

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Plant-based heterologous expression systems can be leveraged to produce high-value therapeutics, industrially important proteins, metabolites, and bioproducts. The production can be scaled up, free from pathogen contamination, and offer post-translational modifications to synthesize complex proteins. With advancements in molecular techniques, transgenics, CRISPR/Cas9 system, plant cell, tissue, and organ culture, significant progress has been made to increase the expression of recombinant proteins and important metabolites in plants. Methods are also available to stabilize RNA transcripts, optimize protein translation, engineer proteins for their stability, and target proteins to subcellular locations best suited for their accumulation. This mini-review focuses on recent advancements to enhance the production of high-value metabolites and proteins necessary for therapeutic applications using plants as bio-factories.

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“…The CRISPR/Cas9 system is a powerful gene-editing tool, which is also used to generate A. belladonna plants with high-yield hyoscyamine ( Zeng et al, 2021 ). Hyoscyamine is converted to anisodamine, and anisodamine to scopolamine under catalysis of H6H ( Hashimoto and Yamada, 1986 ).…”

Section: Engineering Medicinal Tropane Alkaloid Production In Plantsmentioning

confidence: 99%

Biotechnological Approaches on Engineering Medicinal Tropane Alkaloid Production in Plants

Gong

Lan³

et al. 2022

Front. Plant Sci.

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Hyoscyamine and scopolamine, belonging to medicinal tropane alkaloids (MTAs), are potent anticholinergic drugs. Their industrial production relies on medicinal plants, but the levels of the two alkaloids are very low in planta. Engineering the MTA’s production is an everlasting hot topic for pharmaceutical industry. With understanding the MTA’s biosynthesis, biotechnological approaches are established to produce hyoscyamine and scopolamine in an efficient manner. Great advances have been obtained in engineering MTA’s production in planta. In this review, we summarize the advances on the biosynthesis of MTAs and engineering the MTA’s production in hairy root cultures, as well in plants. The problems and perspectives on engineering the MTA’s production are also discussed.

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Development of Atropa belladonna L. Plants with High-Yield Hyoscyamine and without Its Derivatives Using the CRISPR/Cas9 System

Cited by 32 publications

References 36 publications

Integrating Metabolomics and Transcriptomics to Unveil Atisine Biosynthesis in Aconitum gymnandrum Maxim

Integrating Metabolomics and Transcriptomics to Unveil Atisine Biosynthesis in Aconitum gymnandrum Maxim

Plant-based expression platforms to produce high-value metabolites and proteins

Biotechnological Approaches on Engineering Medicinal Tropane Alkaloid Production in Plants

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