Abstract

Taxol is one of the most potent and effective anticancer drugs and is originally isolated from Taxus species. To investigate the specific regulatory mechanisms of taxol synthesis in Taxus wallichiana var. mairei, RNA-seq was conducted to reveal the differences in transcriptional levels between wild type (WT) and “Jinxishan” (JXS), a cultivar selected from a population of Taxus mairei that shows about 3-fold higher taxol content in the needles than WT. Our results indicated that high expressions of the genes taxadienol acetyltransferase (TAT), taxadiene 5-alpha hydroxylase (T5H), 5-alpha-taxadienol-10-beta-hydroxylase (T10OH), and 2-debenzoyl-7,13-diacetylbaccatin III-2-O-benzoyl-transferase (DBBT), which catalyze a series of key acetylation and hydroxylation steps, are the main cause of high taxol content in JXS. Moreover, in the present study, the activation of jasmonic acid (JA) signal transduction and its crosstalk with gibberellin (GA), auxin, and ethylene (ET) explained the elevation of differentially expressed genes (DEGs) from the taxol biosynthesis pathway. This also indicates that taxol biosynthesis in T. mairei is associated with the balance of cell development and defense. TF-encoding (transcriptional factor) genes, represented by the ethylene-responsive transcription factor (ERF), basic/helix-loop-helix (bHLH), MYB, and WRKY families, were detected as differentially expressed between JXS and WT, further indicating that the regulation of hormone signaling on taxol biosynthesis genes was mediated by transcription factors (TFs). To our knowledge, this is the first study to illustrate the regulatory mechanisms of taxol synthesis in a new cultivar of T. mairei with a high taxol content in its needles. These transcriptome data provide reasonable explanations for the variation of taxol content between WT and JXS.

Highlights

  • Taxol, originally isolated from the bark of Taxus brevifolia [1], is one of the most effective antitumor drugs for the treatment of several cancers, such as breast, lung, and ovarian cancers [2]

  • Our results showed that two unigenes in the biosynthesis of jasmonic acid (JA), linoleate 9S-lipoxygenase (LOX), and oxophytodienoate reductase (OPR) showed increased transcript abundance in JXS

  • Our results showed a differential expression of several transcription factors (TFs)-encoding genes, including ethylene-responsive transcription factor (ERF), bHLH, MYB, and WRKY, between JXS and wild type (WT), which may be involved in the regulation of genes in the taxol biosynthesis pathway

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Summary

Introduction

Originally isolated from the bark of Taxus brevifolia [1], is one of the most effective antitumor drugs for the treatment of several cancers, such as breast, lung, and ovarian cancers [2]. In addition to screening for Taxus species with high levels of taxol [4], several alternative methods have been explored, such as total synthesis of taxol [5], plant cell culture [6], and taxol-producing fungi [7]. Most of these methods are difficult to scale because of the large quantity of organic solvents consumed and low efficiency. For the foreseeable future, Taxus species will remain a source for taxol and related precursors. The supply of taxol and its precursors will undoubtedly depend on understanding the taxol biosynthesis pathway

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