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Heterocyclic Drugs from Plants
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Valeria Garcia, Felipe Gonzalez
Docetaxel better recognizes as Taxotere, is a heterocyclic plant-derived anticancer drug that is frequently used to treat cancers like stomach, lung (NSCLC) breast, brain, prostate, and others (General Cancer Information, 2016). Docetaxel is a semi-synthetic product of taxol (paclitaxel), separated from the bark of Pacific yew (Taxus brevifolia) giving insight as to its brand name taxotere. Taxol (paclitaxel) is commonly extracted from Taxus brevifolia and is required to treat ovarian, breast, and NSCLC. Paclitaxel can also treat AIDS-related Kaposi sarcoma (Paclitaxel, 2018). Both docetaxel and paclitaxel belong to ‘taxanes’ which is a diterpene class having a taxadiene core (Zhao et al., 2012). Taxanes are very efficient anticancer drugs. In contrast, diterpenes belong to a class called ‘terpenoids.’ Docetaxel is a frontline anticancer chemotherapeutic agent in this era (Choi et al., 2015).
Conversion of Natural Products from Renewable Resources in Pharmaceuticals by Cytochromes P450
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Giovanna Di Nardo, Gianfranco Gilardi
In another study, the first steps in taxol biosynthesis (Fig. 17.6) were engineered in E. coli. A multivariate modular approach was used to optimize the isoprenoid pathway taking into account the enzymes that constitute the limiting steps and modulating their expression. The pathway was divided into two modules, the first one (methylerythritol-phosphate (MEP) pathway) producing the two building blocks, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). In the second module, co-expression of geranylgeranyl pyrophosphate (GGPP) and taxadiene synthase led to the production of 1 g/L of taxadiene in fed-batch bioreactor fermentations. Moreover, the cytochrome P450 acting as taxadiene-5α-hydroxylase (Jennewein et al., 2004) was fused with its redox partner cytochrome P450 reductase (CPR) to create a self-sufficient protein leading to the production of the taxol precursor taxadien-5α-ol at a concentration of approximately 60 mg/L (Ajikumar et al., 2010). First steps of taxol biosynthesis that were successfully reached through biocatalytic approaches.
Taxines
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Besides taxines (which are poisonous alkaloids of yew tree), taxanes (or taxoids) are a class of diterpenoid drugs derived from yew tree or synthesized artificially that feature a taxadiene core and have the capacity to inhibit cancer cell growth and division (e.g., Taxol A/paclitaxel, Taxol B/cephalomannine, docetaxel, abraxane, cabazitaxel). Docetaxel is a semisynthetic taxane from the needles of T. baccata; braxane is a nanoparticle albumin-bound paclitaxel; and cabazitaxel is a semisynthetic derivative of docetaxel for the treatment of prostate cancer in docetaxel-refractory clinical settings (Figure 106.3) [7].
Human gut microbiome aging clocks based on taxonomic and functional signatures through multi-view learning
Published in Gut Microbes, 2022
Yutao Chen, Hongchao Wang, Wenwei Lu, Tong Wu, Weiwei Yuan, Jinlin Zhu, Yuan Kun Lee, Jianxin Zhao, Hao Zhang, Wei Chen
Among these identified biomarkers, we found that many of the species and pathways showed specific trends with age. For example, F. magna, B. dentium, and Clostridium clostridioforme had increased abundance in the elderly, while P. copri and Burkholderialse bacterium 1_1_47 decreased in abundance with age (Figure 6b). Similar age distribution characteristics were observed in metabolic pathways; acetyl-CoA biosynthesis, nicotinate degradation and L-leucine degradation had a higher probability of enrichment in the gut with increasing age. In contrast, taxadiene biosynthesis, tRNA processing and L-isoleucine biosynthesis had a high possibility of function loss with increasing age (Figure 6c).