Frontiers in Natural Product Chemistry: Volume 5

Atta-ur-Rahman

• Éditeur: Bentham Science Publishers
• Année: 2019
• ISBN:
  9789811423772
• Sujet: Medicine
• Sous-sujet: Pharmacology

Frontiers in Natural Product Chemistry is a book series devoted to publishing monographs that highlight important advances in natural product chemistry. The series covers all aspects of research in the chemistry and biochemistry of naturally occurring compounds, including research on natural substances derived from plants, microbes and animals. Reviews of structure elucidation, biological activity, organic and experimental synthesis of natural products as well as developments of new methods are also included in the series.
The fourth volume of the series brings seven reviews covering these topics:
-natural antiamoebic medicines, analgesics and antimalarials
-essential oils and cognitive performance
-cannabis and drug development
-lectins in biosensors,
-brassinosteroids.

Overview of Past and Present Developments Towards Biotechnological and Molecular Approaches to Improve Taxol Production

Samavia Mubeen¹, Chun-Tao He¹, Bilal Ahmad Asad², Zhong-Yi Yang^{1, *}

¹ State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Xingang Xi Road 135, Guangzhou, 510275, China

² State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100081, China

Abstract

Taxol (paclitaxel) is one of the most used chemotherapeutic drugs, first isolated from Pacific yew tree T. brevifolia. It is used for several cancer treatments due to its unique mechanism of action. The demand for taxol supply was exceeded significantly due to its low accumulation in Taxus sp., slow growth of the tree and high cost of extraction. Due to these reasons, considerable efforts have been carried out to explore the alternative sources, including plants other than Taxus sp., total and semi-synthesis of taxol, plant cell culture technology, and endophytic fungi. The biosynthesis of taxol is a complex pathway and several genes associated with taxol biosynthesis are identified and cloned. Transcriptomic studies of the critical genes involved in taxol biosynthesis pathway provided valuable insight in gene regulation patterns about metabolite synthesis. Also, recent advances in metabolic engineering have demonstrated the potential of genes regulation to increase taxol production. This chapter provides a more in-depth insight into basic and applied research to increase taxol production.

Keywords: Biosynthetic pathway, Cancer treatment, Metabolic engineering, Natural products, Secondary metabolites, Taxol, Taxus, Taxol production, Taxanes, Taxol toxicity.

---

^* Corresponding author Zhong-Yi Yang: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Xingang Xi Road 135, Guangzhou, 510275, China; Tel: [phone]; E-mail: [email protected]

1. INTRODUCTION

“Natural products” also called “secondary metabolites” are organic molecules of low molecular weight (often less than 3,000 Daltons) with particular and exceptionally complex structures. The significant number of these substances
don't take part in the development and growth of the plant [1]. These substances assist the plants in survival by providing a defense mechanism against predators, and it also helps the plants to adapt their surrounding environment. Nevertheless, despite their importance for the plant itself, various secondary metabolites are also of great incentive to the human on account of their attractive natural and therapeutic activities [2^-4]. From the beginning of human civilization, these vital organic substances of different plants have been used to treat diverse types of diseases. Indeed, at present plants are considered as the most significant source of natural drug compounds, and these substances constitute around 25% of the prescribed medication [5].

Natural products also used as chemotherapeutic agents either in natural and synthetic modified forms [6]. One-third of the anti-cancer agents used in medicine are natural products or their derivatives and produced on information that picked up from micro and macromolecules that exist in nature. Since 1940, food and drug administration (FDA) approved more than 140 anti-cancer agents for cancer treatment, among them, 60% are derived from natural products [7]. Natural product based cancer drugs that are involved in war against cancer include taxanes (paclitaxel, docetaxel), vinca alkaloids (vindesine, vincristine, vinorelbine, vinblastine), camptothecin and its derivatives (irinotecan, topotecan), anthracyclines (idarubicin, doxorubicin, epirubicin, daunorubicin), podophyllotoxin and its derivative (teniposide, etoposide) and others [8, 9]. ‘Taxol’ (generic name paclitaxel) is a most promising complex diterpene, alongside baccatin III (BAC III) and 10-deacetylbaccatin III (10-DAB III), widely used for cancer treatment. It is used to treat different types of cancer including breast cancer [10, 11], ovarian carcinomas [12, 13], skin cancer [14], and non-small cell lung cancer [15]. It is also used to treat neurodegenerative diseases such as Alzheimer's [16, 17] and also a useful compound for the drug-eluting coronary artery stents [18], and polycystic kidney disease [19]. Moreover, taxol was found effective against restenosis [20], psoriasis [21], and tauopathies [22] that require microtubules stabilization.

This chapter aims to summarize the current information available regarding the taxol development as drug and how it works to kill the cancer cells. We considered the recent progress in taxol production and also focused on optimizing strategies to improve taxol and related taxane obtained from the different sources for cheaper commercial production of taxol. Besides, we also cover the metabolic engineering strategies related to the microorganisms, heterologous plants, and Taxus cell cultures, to improve taxoids production. We also described the advances in molecular biology and genomics, which were made to overcome the gap in our knowledge of the taxol and other related taxoids biosynthesis. However, this chapter does not summarize the complete range of such published research studies.

2. TAXOL AND ITS SUCCESS STORY TO DRUG DEVELOPMENT

An open screening center named National cancer institute (NCI) was established by Cancer chemotherapy nati...