Taxoids biosynthesis

Encouraged by the success of BTH, a large number of benzothiadiazole derivatives were developed. New synthetic elicitors that showed powerful eliciting activities on taxoid biosynthesis by Taxus chinensis cell suspension cultures were obtained as shown in Figure 7.7. JA and JA derivatives... 

Terpenoids with heterocyclic fragments as bioactive taxoids from Japanese yew Taxsus cuspidata and taxol biosynthesis 98H(47) 1111. 

Taxol is biosynthesized in 19 steps from GGPP that originates from precursors of the MEP pathway (Fig. 5). The biosynthesis of Taxol begins with the formation of the tricyclic diterpene skeleton of taxa-4(5),ll(12)-diene (17, 39). All genes for the enzymes in this early pathway have been identified in Taxus cuspidata and a taxa-4(5),ll(12)-diene synthase has been identified in several Taxus species. The mechanism of this di-TPS has been explored in detail (39). Taxa-4(5),ll(12)-diene is then hydroxylated by several cytochrome P450 taxoid oxygenases to yield a putative intermediate decorated with seven alcohol... 

Walker, K., Long, R., Croteau, R.,The final acylation step in taxol biosynthesis cloning of the taxoid C13-side-chain... 

This material was further resolved by LH-20 (chloroform-methanol, 1 1). Bioassay guided purification of these fractions will continue imtil the chemical promoter(s) responsible for titer augmentation are isolated and characterized. This has proven more difficult than expected because the broth extracts are a complex mixture. Each column fraction must be tested in triplicate at several different concentrations, because a taxoid promoter may actually depress production if added at too high of a concentration. If the concentration is too low, then the actuating threshold may not be reached. Finding the proper test concentration for each extract is a slow process. With time, the process may yield an effective promoter of fungal taxol biosynthesis. 

Chau M, Croteau R (2004) Molecular cloning and characterization of a cytochrome P450 taxoid 2a-hydroxylase involved in Taxol biosynthesis. Arch Biochem Biophys 427 48-57... 

Biosynthesis Clinical trial Docetaxel Paclitaxel Taxoids Toxicology... 

Proteomics and metabolomics are thus key technologies in non-model plants for linking genes involved in the respective pathways with biosynthesis and accumulation of the natural compoimd. Huge efforts are presently invested in the elucidation of the biosynthetic pathways of anticancer (e.g. vinblastin in Catharanthus roseus or taxoids in Taxus baccata), antimalar-ial (artemisinin in Artemisia annua) drugs, or painkillers (e.g. morphine in the opium poppy) on different continents, supported by national and international programs. 

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