Transcriptome and comparative chloroplast genome analysis of Taxus yunnanensis individuals with high and low paclitaxel yield

Paclitaxel has been isolated from the bark of Taxus brevifolia since 1967 and has been used as an anti-cancer drug for the treatment of various cancers such as breast cancer, lung cancer, and ovarian cancer (Weaver, 2014). However, owing to the destructive harvesting at production sites, the complex purification process, and low yield, the supply of paclitaxel remains far from meeting market demand (Mutanda et al., 2021). To increase the yield of paclitaxel, a paclitaxel total synthesis method has been reported (Nicolaou et al., 1994). However, its complex synthesis process leads to a decrease in yield, an increase in cost, and the production of various toxic products, making this method difficult to commercialize (Ahmed Khalil et al., 2022). After elucidating the total synthesis method of paclitaxel, a semi-synthesis method was also published, starting from a high-content paclitaxel intermediate, such as 10-deacetyl baccatin III (10-DAB), to chemically synthesize paclitaxel (Baloglu and Kingston, 1999). Later, Chen et al. (Chen et al., 2003) isolated endophytic fungi that can produce paclitaxel from the branches and bark of T. yunnanensis, but of the two viable commercial production schemes, semi-synthesis (Kingston et al., 1994) and biosynthesis (Kolewe et al., 2008), semi-synthesis production still relies on plant materials (Li et al., 2015). Existing research shows that the difference in expression of key genes is responsible for the difference in content of paclitaxel and paclitaxel intermediates among different species (Yu et al., 2021), so identifying high-paclitaxel-yield individuals is an important direction for optimizing production.

自1967年以来，科研人员已从短叶红豆杉（Taxus brevifolia）的树皮中分离得到紫杉醇（Paclitaxel），并将其作为抗癌药物用于乳腺癌、肺癌、卵巢癌等多种癌症的治疗（Weaver, 2014）。然而，由于生产环节的破坏性采伐、复杂的纯化工艺以及极低的产率，紫杉醇的供给仍远无法满足市场需求（Mutanda et al., 2021）。为提高紫杉醇的产率，已有研究报道了紫杉醇全合成方法（Nicolaou et al., 1994），但该方法的合成流程极为繁琐，会导致产率下降、成本升高，且会产生多种有毒副产物，难以实现商业化应用（Ahmed Khalil et al., 2022）。在阐明紫杉醇全合成路径后，科研人员又开发了半合成方法：以10-去乙酰巴卡亭III（10-deacetyl baccatin III，10-DAB）等高含量紫杉醇中间体为起始原料，通过化学手段合成紫杉醇（Baloglu and Kingston, 1999）。后续，Chen等人（Chen et al., 2003）从云南红豆杉（T. yunnanensis）的枝条与树皮中分离得到可产生紫杉醇的内生真菌。但在目前两种可行的商业化生产方案——半合成法（Kingston et al., 1994）与生物合成法（Kolewe et al., 2008）——中，半合成生产仍依赖植物原料（Li et al., 2015）。现有研究表明，不同物种间紫杉醇及紫杉醇中间体含量的差异，源于关键基因的表达量差异（Yu et al., 2021），因此筛选高紫杉醇产率的个体是优化生产的重要方向。