Paclitaxel biosynthetic pathway

Fig. 7.3 Taxol/paclitaxel biosynthetic pathway. (Top) ations mediated by members of the CYP725A subfamily.

Figure 8.4 Paclitaxel biosynthetic pathway. TS taxadiene synthase TYHSa taxa-diene 5a-hydroxylase TAT taxadien-5a-ol 0-acetyl transferase TYHIO taxane 10 -hydroxylase TYH14 taxoid 14 -hydroxylase TBT taxane 2a-0-benzoyltransferase DBAT ...

Expression of eight genes in the early part of paclitaxel biosynthetic pathway [85] Pathway enzyme Saccharomyces cerevisiae 1 mgl" of taxadiene 25 pgl" of taxadine-5 -ol... 

Figure 12.5 The biosynthetic pathway for paclitaxel and related taxanes [89]...

Figure 5.25 Simplified schematic representation of the semisynthetic and biosynthetic pathways for producing paclitaxel.

Figure 2.20 Biosynthetic pathway from taxa-4,11-dien to paclitaxel.

Among the worldwide total of 30000 known natural products, about 80% stems from plant resources. The number of known chemical structures of plant secondary metabolites is four times the number of known microbial secondary metabolites. Plant secondary metabolites are widely used as valuable medicines (such as paclitaxel, vinblastine, camptothecin, ginsenosides, and artemisinin), food additives, flavors, spices (such as rose oil, vanillin), pigments (such as Sin red and anthocyanins), cosmetics (such as aloe polysaccharides), and bio-pesticides (such as pyrethrins). Currently, a quarter of all prescribed pharmaceuticals compounds in industrialized countries are directly or indirectly derived from plants, or via semi-synthesis. Furthermore, 11% of the 252 drugs considered as basic and essential by the WHO are exclusively derived from plants. According to their biosynthetic pathways, secondary metabolites are usually classified into three large molecule families phenolics, terpenes, and steroids. Some known plant-derived pharmaceuticals are shown in Table 6.1. 

Overexpression of 9-cis-epoxycarotenoid dioxygenase [79] Enzyme in the absdsic acid (ABC) biosynthetic pathway T. chinensis cell suspension 1.2-fold increase in absdsic acid 2.8-fold increase in paclitaxel... 

Production of artemisinin and paclitaxel precursors by engineered whole-cell biocatalysts from glucose. Introduction of biosynthetic genes from Artemisia annua encoding the amorphadiene synthase and amorphadiene oxidase yielded microbial strains that produce arte-misinic acid. Artemisinic acid can be chemically converted into artemisinin, introduction of the Taxus genes encoding taxadiene synthase and taxadiene 5a-hydroxy-lase resulted in E. constrains that produce key paclitaxel intermediates. The biosynthetic pathway for paclitaxel has not been fully elucidated. 

Several p-amino acids occur naturally as free metabolites in metabolic pathways or as key intermediates in biosynthetic products. p-Alanine is the simplest p-amino acid that appears in pantothenic acid, a precursor of the coenzyme A. Further examples are (2R,3S)-N-benzoyl-3-phenylisoserine derived from (R)-p-phenylalanine, a compound in the antitumor agent paclitaxel from Taxus brevifolia [89], or as building blocks for p-lactam antibiotics [90] and in jasplakinolide, an antifungal compound [91] (Scheme 29.12). 

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