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Establishment of production platform of camptothecin and homoharringtonine (4/4)

  • Date of declaration:2012-04-20
  • PI:Shu-Hwa Chang
  • Division:Silviculture Division
Research title
Science and Technology Programs(2012)
執行成果摘要
Nothapodytes nimmoniana trees, a major source of camptothecin (CPT) that is a precursor to synthesize anticancer drug, have been created a great profit in biotech company in Taiwan. The process of traditional management begins to plant trees for 5 years and harvest trunks to extract CPT. The branches are discarded. We selected some chemical races of N. nimmoniana that contains high concentration CPT and its analogues, and develop a sustainable management system by harvesting branches annually. To mass producing these few superior clones, tissue culture is the best step. Once more clonal plants are propagated in vitro, we will established a scion garden to produce cutting plants. Plantations established in these two sources will be compared in cost and efficiency. In farm management we will analyze the variation and concentrations of CPT analogus in fresh and different drying/powdering treated branches to find the best yield of both biomass and CPT analogus. In 2012, we harvest 186 kg of branches, drying in 3 different water contents. They were extracted by a commercial chemical plant. According the extracts, we estimated a production of CPT and MCPT was 4.2-5.9 kg/ha/yr, and 0.5-3.4 kg/ha/yr, irrespectively. It indicates that branch harvest system once a year is commercial feasible. Seed harvest this year is 110 kg, greater than did last year (98 kg). Hairy roots grow rapidly in both flasks and 2-L bioreactor.
Homoharringtonin (HHT), found in slow growing Cephalotaxus species, has proven to be an effective drug to cure leukemia cancer. The drug market is expecting to be above 1.3 billion US dollars. Cephalotaxus wilsoniana is scarcely scattered in the mountains of Taiwan.
We found the branches of some mother trees grown in wild contain high concentration of HHT 2-3 times greater than foreign species. Using UPLC analysis we found cephalotaxine, a precursor of HHT, is high level in branches. Some trees contain 3497-8895 ppm, could be a good sources to transform into HHT by semichemical synthesis.