Towards Metabolic Engineering of Podophyllotoxin Production

Seegers, Christel L. C.; Setroikromo, Rita; Quax, Wim J.

doi:10.5772/67615

Cited by 6 publications

(3 citation statements)

References 90 publications

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“…Anhydropodorhizol is structurally linked to yatein, which is a precursor of DPT [23,24]. Therefore, it could be of interest to increase the DPT yields by pathway engineering aimed at converting anhydropodorhizol to DPT [25]. Table 1).…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic Deoxypodophyllotoxin Can Be Extracted in High Purity from Anthriscus sylvestris Roots by Supercritical Carbon Dioxide

et al. 2017

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Deoxypodophyllotoxin is present in the roots of . This compound is cytotoxic on its own, but it can also be converted into podophyllotoxin, which is in high demand as a precursor for the important anticancer drugs etoposide and teniposide. In this study, deoxypodophyllotoxin is extracted from roots by supercritical carbon dioxide extraction. The process is simple and scalable. The supercritical carbon dioxide method extracts 75 - 80% of the total deoxypodophyllotoxin content, which is comparable to a single extraction by traditional Soxhlet. However, less polar components are extracted. The activity of the supercritical carbon dioxide extract containing deoxypodophyllotoxin was assessed by demonstrating that the extract arrests A549 and HeLa cells in the G/M phase of the cell cycle. We conclude that biologically active deoxypodophyllotoxin can be extracted from by supercritical carbon dioxide extraction. The method is solvent free and more sustainable compared to traditional methods.

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Section: Resultsmentioning

confidence: 99%

Cytotoxic Deoxypodophyllotoxin Can Be Extracted in High Purity from Anthriscus sylvestris Roots by Supercritical Carbon Dioxide

et al. 2017

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“…Another alternative explored have been cell suspension cultures but produce only small amounts of PTOX (max. 0.65% dry weight) (Seegers et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Accumulation of podophyllotoxin in root culture of Hyptis suaveolens (L.) Poit: a potential natural lignan for clinically useful anticancer drugs

Silva

Assis

Coelho

et al. 2023

Preprint

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Podophyllotoxin (PTOX) is a natural antiviral, antirheumatic and anticancer molecule but its chemical synthesis is expensive. The present study aimed to develop and validate an analytical method by HPLC for the quantification of PTOX in roots of Hyptis suaveolens, as well as to evaluate the culture of its roots in vitro in liquid medium supplement with different concentrations of Indole-3-butyric acid (IBA), 1-Naphthaleneacetic acid (NAA), vitamins and myo-inositol. The analytical method was developed and validated. Root culture was used for biomass production and PTOX content was quantified using the developed analytical method after successful validation. The parameters that confirmed the analytical method were selectivity (peak purity: > 99%), system suitability (Rs = 2.92; N = 7064; k = 1.23; As = 1.31; DPR = 0.61%), intra-day and inter-day precision (DPR = 2.43% and 2.96%, respectively), linearity (R² = 0.997), recovery percentage (90.47–101.85%), limit of quantification (5.25 ng) and limit of detection (0.5 ng). Root culture in MS medium containing 1 mg L-1 IBA + 0.5 mg L-1 NAA showed the highest root dry weight (248.76 mg) and the highest PTOX concentration in the root (179, 97 µg-1). The vitamins and myo-inositol in the medium produced 198.88 mg of root dry weight and 6.01 µg g-1 of PTOX. The roots cultured in liquid MS medium supplemented with 1 mg L-1 of IBA + 0.5 mg L-1 of NAA maximized the root biomass and PTOX content. The adequate balance of vitamin and myo-inositol supplementation in liquid MS culture medium increased the production of root dry weight and PTOX accumulation.

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“…Therefore, much attention has been focused on biosynthesis and bioproduction of podophyllotoxin and related compounds in Podophyllum spp. and other plant species (Bhattacharyya et al 2016;Kumar 2017;Kumari et al 2014;Sasheva and Ikonkova 2017;Seegers et al 2017;Suzuki and Umezawa 2007).…”

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De novo transcriptome analysis of needles of Thujopsis dolabrata var. hondae

Suzuki

Tanaka

et al. 2019

Plant Biotechnology

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Podophyllotoxin is a starting material of the semisynthetic anticancer medicines etoposide, teniposide, and etopophos. The major plant source of podophyllotoxin is rhizomes of Podophyllum hexandrum, which is a Himalayan endangered species; therefore, alternative sources of podophyllotoxin or bioproduction systems have been pursued to avoid exploiting this limited natural resource. In this paper, we report de novo transcriptome analysis of Thujopsis dolablata var. hondae, which accumulates the podophyllotoxin derivatives (deoxypodophyllotoxin and β-peltatin A methyl ether) in its needles. We analyzed transcriptomes of the T. dolablata var. hondae young needles to obtain the sequences that putatively encode O-methyltransferases, cytochrome P450s, and a 2-oxoglutarate dependent dioxygenase because these protein families are responsible for podophyllotoxin-related compound formation in P. hexandrum. The resulting transcriptomes contained considerable numbers of coding sequences classified into the three protein families. Our results are a genetic basis for identifying genes involved in the biosynthesis of podophyllotoxin and related compounds and also for future metabolic engineering of podophyllotoxin in heterologous hosts.

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Towards Metabolic Engineering of Podophyllotoxin Production

Cited by 6 publications

References 90 publications

Cytotoxic Deoxypodophyllotoxin Can Be Extracted in High Purity from Anthriscus sylvestris Roots by Supercritical Carbon Dioxide

Cytotoxic Deoxypodophyllotoxin Can Be Extracted in High Purity from Anthriscus sylvestris Roots by Supercritical Carbon Dioxide

Accumulation of podophyllotoxin in root culture of Hyptis suaveolens (L.) Poit: a potential natural lignan for clinically useful anticancer drugs

<i>De novo</i> transcriptome analysis of needles of <i>Thujopsis dolabrata</i> var. <i>hondae</i>

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