A novel step towards the heterologous biosynthesis of paclitaxel: Characterization of T1βOH taxane hydroxylase.

In the quest for innovative cancer therapeutics, paclitaxel remains a cornerstone in clinical oncology. However, its complex biosynthetic pathway, particularly the intricate oxygenation steps, has remained a puzzle in the decades following the characterization of the last taxane hydroxylase. The high divergence and promiscuity of enzymes involved have posed significant challenges.

Overexpression of BAPT and DBTNBT genes in Taxus baccata in vitro cultures to enhance the biotechnological production of paclitaxel.

Paclitaxel is one of the most effective anticancer drugs ever developed. Although the most sustainable approach to its production is provided by plant cell cultures, the yield is limited by bottleneck enzymes in the taxane biosynthetic pathway: baccatin-aminophenylpropanoyl-13-O-transferase (BAPT) and 3'-N-debenzoyltaxol N-benzoyltransferase (DBTNBT). With the aim of enhancing paclitaxel production by overcoming this bottleneck, we obtained distinct lines of Taxus baccata in vitro roots, each independently overexpressing either of the two flux-limiting genes, BAPT or DBTNBT, through a Rhizobium rhizogenes A4-mediated transformation.

Polyploidy as a strategy to increase taxane production in yew cell cultures: Obtaining and characterizing a Taxus baccata tetraploid cell line.

Novel approaches to optimize the production of plant specialized metabolites are crucial to reach maximum productivity of plant biofactories. Plant polyploidization frequently enhances protein synthesis and thereby increases the biosynthesis of specialized metabolites. Paclitaxel is a valuable anticancer agent scarcely produced in nature.

Genetic approaches in improving biotechnological production of taxanes: An update.

Paclitaxel (PTX) and its derivatives are diterpene alkaloids widely used as chemotherapeutic agents in the treatment of various types of cancer. Due to the scarcity of PTX in nature, its production in cell cultures and plant organs is a major challenge for plant biotechnology. Although significant advances have been made in this field through the development of metabolic engineering and synthetic biology techniques, production levels remain insufficient to meet the current market demand for these powerful anticancer drugs.

Insights into the control of taxane metabolism: Molecular, cellular, and metabolic changes induced by elicitation in cell suspensions.

More knowledge is needed about the molecular/cellular control of paclitaxel (PTX) production in spp. cell cultures. In this study, the yield of this anticancer agent in cell suspensions was improved 11-fold after elicitation with coronatine (COR) compared to the untreated cells, and 18-fold when co-supplemented with methyl-β-cyclodextrins (β-CDs).

The Epigenetic Regulation in Plant Specialized Metabolism: DNA Methylation Limits Paclitaxel Biotechnological Production.

Environmental conditions are key factors in the modulation of the epigenetic mechanisms regulating gene expression in plants. Specifically, the maintenance of cell cultures in optimal conditions alters methylation patterns and, consequently, their genetic transcription and metabolism. Paclitaxel production in cell cultures is reduced during its maintenance in conditions, compromising the biotechnological production of this valuable anticancer agent.

Methyl-β-cyclodextrin and coronatine as new elicitors of tropane alkaloid biosynthesis in Atropa acuminata and Atropa belladonna hairy root cultures.

Hyoscyamine (HYO) and scopolamine (SCO) are tropane alkaloids acting as anticholinergic factors on the parasympathetic nervous system in humans and are produced by Solanaceous plants. Two strains of Agrobacterium rhizogenes, A4 and LBA9402, were used to infect Atropa acuminata Royle ex Miers and Atropa belladonna L. leaf explants.

Improved biotechnological production of paclitaxel in Taxus media cell cultures by the combined action of coronatine and calix[8]arenes.

Paclitaxel (PTX), a widely used anticancer agent, is found in the inner bark of several Taxus species, although at such low levels that its extraction is ecologically unsustainable. Biotechnological platforms based on Taxus sp. cell cultures offer an eco-friendlier approach to PTX production, with yields that can be improved by elicitation.

A Novel Hydroxylation Step in the Taxane Biosynthetic Pathway: A New Approach to Paclitaxel Production by Synthetic Biology.

Engineered plant cell lines have the potential to achieve enhanced metabolite production rates, providing a high-yielding source of compounds of interest. Improving the production of taxanes, pharmacologically valuable secondary metabolites of spp., is hindered by an incomplete knowledge of the taxane biosynthetic pathway.

Transfecting Taxus � media Protoplasts to Study Transcription Factors BIS2 and TSAR2 as Activators of Taxane-Related Genes.

Taxane diterpenes are secondary metabolites with an important pharmacological role in the treatment of cancer. Taxus spp. biofactories have been used for taxane production, but the lack of knowledge about the taxane biosynthetic pathway and its molecular regulation hinders their optimal function.

Biotechnological production of ruscogenins in plant cell and organ cultures of Ruscus aculeatus.

Ruscus aculeatus is a threatened medicinal plant whose main bioactive components, the ruscogenins, have long been used in the treatment of hemorrhoids and varicose veins, but recently demonstrated activity against some types of cancer. Plant cell biofactories could constitute an alternative to the whole plant as a source of ruscogenins. In this pipeline, despite the in vitro recalcitrance of R.

Genomic methylation in plant cell cultures: A barrier to the development of commercial long-term biofactories.

Plant cell biofactories offer great advantages for the production of plant compounds of interest, although certain limitations still need to be overcome before their maximum potential is reached. One obstacle is the gradual loss of secondary metabolite production during in vitro culture maintenance, which is an important impediment in the development of large-scale production systems. The relationship between in vitro maintenance and epigenetic changes has been demonstrated in several plant species; in particular, methylation levels have been found to increase in in vitro cultures over time.

Advances in the Regulation of In Vitro Paclitaxel Production: Methylation of a Y-Patch Promoter Region Alters BAPT Gene Expression in Taxus Cell Cultures.

Plant cell biofactories represent a promising solution to the increasing demand for plant-derived compounds, but there are still limiting factors that prevent optimal production, including the loss of yield during in vitro maintenance. Our results reveal a clear correlation between genomic methylation levels and a progressive decline in taxane production in Taxus spp. cell cultures.

Comparing aryltetralin lignan accumulation patterns in four biotechnological systems of Linum album.

Linum album is a herbaceous plant with medical interest due to its content of podophyllotoxin (PTOX), an aryltetralin lignan with cytotoxic activity. Previous studies in our laboratory showed that cell suspension cultures of L. album produced more PTOX than methoxypodophyllotoxin (6-MPTOX), both lignans being formed from the same precursor after divergence close to the end of the biosynthetic pathway.

Perfluorodecalins and Hexenol as Inducers of Secondary Metabolism in and Cell Cultures.

Plant cell cultures constitute a potentially efficient and sustainable tool for the production of high added-value bioactive compounds. However, due to the inherent restrictions in the expression of secondary metabolism, to date the yields obtained have generally been low. Plant cell culture elicitation can boost production, sometimes leading to dramatic improvements in yield, as well as providing insight into the target biosynthetic pathways and the regulation of the genes involved.

Bioconversion of stilbenes in genetically engineered root and cell cultures of tobacco.

It is currently possible to transfer a biosynthetic pathway from a plant to another organism. This system has been exploited to transfer the metabolic richness of certain plant species to other plants or even to more simple metabolic organisms such as yeast or bacteria for the production of high added value plant compounds. Another application is to bioconvert substrates into scarcer or biologically more interesting compounds, such as piceatannol and pterostilbene.

Viability-reducing activity of Coryllus avellana L. extracts against human cancer cell lines.

The increasing rate of cancer incidence has encouraged the search for novel natural sources of anticancer compounds. The presence of small quantities of taxol and taxanes in Corylus avellana L. has impelled new potential applications for this plant in the field of biomedicine.