Paclitaxel is a famous anti-cancer drug. For the treatment of ovarian cancer, breast cancer and non-small cell lung cancer.
Paclitaxel is one of the more complex natural products, belonging to diterpene, the skeleton has four rings, from left to right are A, B, C, D, of which A, B, C are carbon ring, another D ring is oxetane. Paclitaxel was originally extracted from the bark of Taxus Brevifolia which growing in the U.S., but its content is very low, about 10-50kg of bark can be extracted from one gram of paclitaxel. Do a group of clinical trials need 25000 adult yew trees, and this kind of trees in the world distribution is very small, slow-growing, high-volume logging will make it has endangered risk, which was made paclitaxel become a thorny issue.
According to pharmaceutical raw materials suppliers, paclitaxel has become the world's first selling anticancer drugs currently. At the same time, researchers are doing other clinical trials about the effect of paclitaxel on Alzheimer's disease and other cancers. Currently, methods of human obtaining paclitaxel have: A. natural extract, B. artificially synthesized, C. semi- synthetic, D. biological fermentation. Of which the latter three methods are mostly remained in the laboratory stage.
Paclitaxel biosynthesis
The molecular formula of paclitaxel is C47H51NO14, terpene ring structure natural secondary metabolites. It mainly made by the taxane ring and side chains. Study the biosynthesis for the efficiency of artificially direction and the cloning combinations, gene which forming critical enzyme, improve the yield of paclitaxel has significant meaning. Currently, whether can find one or two key enzymes and make its gene purified and gene cloning is the key of researching. Whether taxus gene cloning can be breakthrough remains to be seen, it stills in the stage of imaginary ways which people have found, at present these technologies are still in the laboratory stage.
Chemical synthesis of paclitaxel
According to the study and reported: 10-deacetylbaccatin b (baccatin b) which isolated from Taxus plants, its activity is obviously lower than paclitaxel, but can be extracted from yew needles. This substance through a four-step chemical process can be synthesized paclitaxel, bring significant progress for solving the new sources way of paclitaxel. However, chemical synthesis from the substantive sense has not yet achieved a complete breakthrough, without application value at present.
Microbial synthesis of paclitaxel
Researchers isolated a kind of parasitic fungus from taxus brevifolia phloem, which can produce paclitaxel and related hydrocarbon compounds in a particular medium, but due to the current low yield, it cannot be applied in production. Recombinant DNA technology is expected to improve the yield of paclitaxel.
By the studies also found that: the yew root is the organ that has the highest paclitaxel content except for bark. People use agrobacterium rhizogenes dipping the yew plant explants to induce rooting. This approach does not need foreign aid hormones, the roots growing rapidly, genetic traits are stable and get more attention. If can combined the synthesis paclitaxel or their similar derivatives, the key enzymes which obtained in microbial biosynthesis with the related genes of cloned yew, this method would get a breakthrough.
Article Source:http://www.cospcn.com
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