Yew fruit Photo courtesy of Zhang Xiao, Tsinghua University
Yew fruit Photo courtesy of Zhang Xiao, Tsinghua University To efficiently synthesize paclitaxel, the star anti-cancer drug with complex molecular structure, humans have to "learn from" the cherished endangered plant yew
On July 15, the Institute of Genomics of the Chinese Academy of Agricultural Sciences (Shenzhen) (hereinafter referred to as the Institute of Genomics) and Hunan Agricultural University jointly published a high-quality reference genome at the chromosome level of Taxus chinensis in Nature-Plants and comprehensively analyzed it.
Unsustainable: Star anti-cancer drugs rely heavily on rare and endangered plants
Unsustainable: Star anti-cancer drugs rely heavily on rare and endangered plants "Plant giant panda" yew is a rare and endangered plant in China, and it is also called "national treasure" by 42 countries around the world
Taxol, a unique diterpene compound produced by yew, was first isolated and identified from the bark of yew in the 1960s
At present, as a star antitumor drug of plant origin with the best known curative effect, paclitaxel can specifically regulate tubulin to inhibit the abnormal division and proliferation of tumor cells.
It is reported that the chemical structure of paclitaxel is extremely complex, containing 47 carbon atoms, 11 stereo centers, multiple chiral centers and functional groups.
"However, the content of paclitaxel in yew is very low, and the growth of yew is very slow, causing the current contradiction between the supply and demand of paclitaxel
"However, there is a lack of guidance from the yew genome data and the taxol biosynthesis pathway has not been fully resolved.
Successfully assembled the chromosome-level genome of Taxus chinensis
Successfully assembled the chromosome-level genome of Taxus chinensis There are 11 species of yew in the world.
According to Xiong Xingyao, a researcher at the Institute of Genomics, Taxus chinensis is mainly distributed in provinces south of the Yangtze River basin, and is mostly distributed in southern provinces of China, including Henan and Shaanxi
The team selected haplotype endosperm materials of Taxus chinensis for whole genome sequencing, and successfully assembled a high-quality reference genome at the chromosome level
Genomic characteristics of Taxus chinensis var.
Genomic characteristics of Taxus chinensis var.
At the same time, "the team's multi-omics research system on tomatoes and cucumbers provides a powerful tool for the analysis of paclitaxel metabolic pathways
The study found that the genome of Taxus chinensis has undergone an ancient whole-genome replication event, and the repetitive sequences in its genome have undergone a long-term and continuous insertion process
Yan Jianbin explained, “The discovery of genome-wide duplication and continuous insertion of repeated sequences explains to a certain extent the reason why the genome of Taxus chinensis has become larger
in the course of evolution.
At the same time, compared with other gymnosperms during the long evolutionary process, Taxus chinensis has evolved to form a unique family of Gypsy and Copia transposons, which reflects the genetic uniqueness of yew as a'plant giant panda' from a genomic perspective
.
"
Revealing the genetic basis of paclitaxel biosynthesis
Revealing the genetic basis of paclitaxel biosynthesis Not only that, yew has also evolved a unique family of genes related to taxol biosynthesis
.
"Taxol can only be synthesized in Taxus chinensis, which is closely related to its unique gene family
.
" Yan Jianbin said that the research system analyzed the location and coordinated expression regulation of genes related to paclitaxel synthesis, and mapped the location of multiple related gene families.
In particular, it revealed the genomic distribution and regulation of the cytochrome P450 family, especially the taxol synthesis-related P450 subfamily (CYP725A)
.
"Whether the taxol synthase gene has a coordinated distribution and regulation on the genome has been unknown before
.
" Yan Jianbin said that their research further found that the taxol synthesis-related gene has an aggregated distribution on the chromosome of Taxus chinensis and is coordinated by the plant hormone jasmin.
Trends, identified the taxus-specific CYP725A family and the first taxol biosynthesis gene cluster consisting of six genes in tandem, and is mainly responsible for catalyzing the first two steps of taxol biosynthesis
.
Professor Deng Zixin, an academician of the Chinese Academy of Sciences, spoke highly of the research progress.
Since the discovery of paclitaxel, scientists have completed more than half a century of research on its structure-activity relationship, drug formulation, drug source, clinical application, and mechanism of action.
Research work
.
Today, Chinese scientists have completed the sequencing and assembly of the Taxus chinensis genome, which provides an important cornerstone for solving the key scientific problem of "How does the yew synthesize taxol"
.
"The distribution and regulation of taxol biosynthesis genes discovered in this research, based on the candidate genes obtained from multi-omics analysis, are of great significance for guiding taxus genetics and breeding and the efficient use of germplasm resources; Paclitaxel synthetic biology biomanufacturing provides biological data assurance, speeds up the design and development of paclitaxel heterogeneous synthesis chassis, and provides a key foundation for the next step in the development of a green, environmentally friendly and sustainable production strategy for paclitaxel biosynthesis
.
" said Deng Zixin
.
The co-first authors of the paper are researcher Xiong Xingyao of the Institute of Genomics, postdoctoral fellow Gou Junbo, research assistant Liao Qinggang, and associate professor Li Yanlin of Hunan Agricultural University
.
Researchers of the Institute of Genomics Yan Jianbin and Huang Sanwen are the co-corresponding authors of the paper
.
The first item funded by the project is marked as the National Key Research and Development Program of Synthetic Biology
.
(Source: China Science News Li Chen)
Related paper information: https://doi.
org/10.
1038/s41477-021-00963-5
https://doi.
org/10.
1038/s41477-021-00963-5
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