Plant Cell Biofactories as In Vitro Production Platforms of the Anticancer Drug Camptothecin

Murali, Sarayu; Rajendran, Hemalatha; Srivastava, Smita

doi:10.1007/978-3-030-58271-5_2

Cited by 1 publication

(3 citation statements)

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“…Although we could account for biomass production, the production of CPT was also an essential objective of our work. To achieve this, we added reactions corresponding to CPT biosynthesis involving the shikimic acid pathway, mevalonic acid pathway, and the methylerythritol pyrophosphate pathway systematically in their respective compartments, as reported by Rather et al (2018) and Murali et al (2021). While performing FBA, we observed that an increase in biomass flux led to a decrease in camptothecin flux, and viceversa.…”

Section: Discussionmentioning

confidence: 97%

“…To achieve this, we added reactions corresponding to CPT biosynthesis involving the shikimic acid pathway, mevalonic acid pathway, and the methylerythritol pyrophosphate pathway systematically in their respective compartments, as reported by Rather et al. (2018) and Murali et al. (2021) .…”

Section: Discussionmentioning

confidence: 99%

“…Several strategies to enhance the production of alkaloids, such as CPT, have been reported ( Murali et al., 2021 ). Some of them include bioprocess optimization strategies, such as elicitation, optimization of media components, and metabolic engineering strategies, such as overexpression of rate-controlling enzymes in the biosynthetic pathway.…”

Section: Introductionmentioning

confidence: 99%

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Genome-scale metabolic model led engineering of Nothapodytes nimmoniana plant cells for high camptothecin production

et al. 2023

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Camptothecin (CPT) is a vital monoterpene indole alkaloid used in anti-cancer therapeutics. It is primarily derived from Camptotheca acuminata and Nothapodytes nimmoniana plants that are indigenous to Southeast Asia. Plants have intricate metabolic networks and use them to produce secondary metabolites such as CPT, which is a prerequisite for rational metabolic engineering design to optimize their production. By reconstructing metabolic models, we can predict plant metabolic behavior, facilitating the selection of suitable approaches and saving time, cost, and energy, over traditional hit and trial experimental approaches. In this study, we reconstructed a genome-scale metabolic model for N. nimmoniana (NothaGEM iSM1809) and curated it using experimentally obtained biochemical data. We also used in silico tools to identify and rank suitable enzyme targets for overexpression and knockout to maximize camptothecin production. The predicted over-expression targets encompass enzymes involved in the camptothecin biosynthesis pathway, including strictosidine synthase and geraniol 10-hydroxylase, as well as targets related to plant metabolism, such as amino acid biosynthesis and the tricarboxylic acid cycle. The top-ranked knockout targets included reactions responsible for the formation of folates and serine, as well as the conversion of acetyl CoA and oxaloacetate to malate and citrate. One of the top-ranked overexpression targets, strictosidine synthase, was chosen to generate metabolically engineered cell lines of N. nimmoniana using Agrobacterium tumefaciens-mediated transformation. The transformed cell line showed a 5-fold increase in camptothecin production, with a yield of up to 5 µg g−1.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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