Pharmaceutically Active Natural Product Synthesis and Supply via Plant Cell Culture Technology

Abstract

The chemical diversity of plant-derived natural products allows them to function in a multitude of ways including flavor enhancers, agricultural chemicals, and importantly, human medicinals. Supply of pharmaceutically active natural products is often a challenge due to the slow growing nature of some species, low yields found in nature, and unpredictable variability in accumulation. Several production options are available including natural harvestation, total chemical synthesis, semisynthesis from isolated precursors, and expression of plant pathways in microbial systems. However, for some medicinal natural products, such as the anticancer agent paclitaxel, where low yields in nature, chemical complexity and lack of knowledge of the complete biosynthetic pathway, preclude many of these options, plant cell culture technology is an attractive alternative for supply. Plant cell suspension cultures are amenable to scale-up, environmental optimization, and metabolic engineering. This review focuses on some of the key challenges in utilizing and commercializing plant cell culture suspension technology, with a focus on pharmaceutically active natural products. Recent research has been directed toward application of traditional strategies such as reactor design, cell immobilization, and enzyme elicitation as well as emerging strategies such as characterizing cellular heterogeneity and variability through flow cytometric techniques, metabolic engineering, and system-wide analysis.

WITHDRAWN: TcJAMYC: A bHLH transcription factor that activates paclitaxel biosynthetic pathway genes in yew

“…Paclitaxel is found in only small quantities in plants, and total synthesis comprises several steps, and is therefore lowyielding. The main current sources of paclitaxel are semi-synthesis from abundant advanced precursors derived from the needles of yew plants and from Taxus suspension cell cultures (2)(3)(4). The biosynthetic pathway leading to paclitaxel has been partially elucidated (5) (Figure 1), but improved understanding of the four or five undefined pathway steps and the overall regulation of paclitaxel synthesis are needed in order to enable bioengineering approaches.…”

Callus Induction and Cellular Suspensions from Murtilla (<i>Ugni molinae</i> Turcz.) for <i>trans</i>-resveratrol Production

“…The comparative studies between in vivo and in vitro material (calli) to quantify secondary metabolites have been conducted for species like Vaccinium macrosporum and Buddleja cordata (Madhavi et al, 1995;Estrada-Zuniga et al, 2009). Presently, however, very few successful examples of the commercial application of cellular suspensions exist due to the low biosynthesis of the compound, differentiation and compartmentalization of cells, lack of developing organelles, unstable cellular lines and the difficulty of scaling production (Kolewe et al, 2008;Estrada-Zuniga et al, 2009).…”

Improved production of chlorogenic acid from cell suspension cultures of <i>Lonicera macranthoids</i>

“…It is shown that more than 60 medicinal plants have higher content of metabolites in culture cells than in original species [11]. In particular, plant cell suspension cultures containing undifferentiated cells are attractive due to their relative similarity to microbial cell culture systems [12]. L. macranthoides Hand.-Mazz.…”