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Key Laboratory of Biosynthesis of Natural Products of National Health and Family Planning Commission

 

The Key Laboratory of Biosynthesis of Natural Products of National Health and Family Planning Commission (the former Ministry of Health Key Laboratory) is affiliated with IMM CAMS&PUMC. The key laboratory was formally established in 1985 on the basis of the Department of Biosynthesis of Natural Products of IMM. In accordance with the requirements of the Ministry of Health, the laboratory was opened while it was constructing. In 1996, the laboratory passed the acceptance inspection organized by the Department of Sciences, Technology and Education of the Ministry of Health. Moreover, the laboratory passed the assessments organized by the same department in 2007 and 2011, respectively.
Professor Zhu Ping serves as the present director of the laboratory. The chairman of the academic committee of the laboratory is Professor Yu De Quan, an academician of the Chinese Academy of Engineering. Currently, the laboratory employs more than 40 staff members and graduate students, including 10 full professors, 3 associate professors, of whom 8 are Ph.D. supervisors and 5 are M.Sc. supervisors.
The main research objective of the laboratory is to study the active substance of natural medicines by modern biotechnology, solve the bottleneck factors of limiting the production and broaden the sources of natural medicines. The other goal of the laboratory is to make the outstanding achievements and cultivate the talent scientists through continuous innovation. The present research is focused on the following aspects: synthetic biology of the scarce and natural medicines, recombinant enzymes of biocatalysis, and the bioactive substances produced by the endophytic microorganisms of the animals and plants, etc. Great progress has been made in the following fields.
1. The laboratory is the first professional group in China to be specialized in the synthetic biology research of paclitaxel and artemisinin. The paper related to taxadiene production by the engineered Saccharomyces cerevisiae was published half a year earlier than the similar research performed by the foreign scientists. The yeast bias codons were used in the studies of the synthetic biology of artemisinic acid for the first time, leading to the significant increase in the yield of armorpha-4,11-diene (a precursor of artemisinic acid) of the engineered yeast. Relevant researches won the third prize of Science and Technology Award for Chinese Pharmaceutical Association in 2011.
2. Through chemo-enzymatically structural modification, several novel taxane-based reversal candidates (e.g. compound NPB-014) towards various multi-drug resistant (MDR) cancer cells have been acquired from our patented compounds, sinenxans, produced by cell cultures of Taxus spp. These candidates exhibit perfect druggability, with 3 times more potent activity than verapamil, a clinical drug, low toxicity, satisfied PK and PD properties, etc. The pharmacological investigations on action mechanism have revealed that they inhibit P-gp and other drug membrane transporters in both expression and function levels. These results suggest that NPB-014 and other compounds are promising for further R & D as MDR reversal agents.
3. Paclitaxel is produced by yew trees at very low concentrations, causing a worldwide shortage of this important anticancer medicine. These plants also produce significant amounts of 7-β-xylosyl-10-deacetyltaxol, which can be bio-converted into 10-deacetyltaxol for semi-synthesis of paclitaxel. To increase the utilization efficiency of the Taxus resource and the clinical supply of paclitaxel, a gene encoding the new glycoside hydrolase was cloned from Lentinula edodes and introduced into the yeast host. The engineered yeast with such a heterologous gene can robustly convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol with the yield of up to 8.42 g/L.
4. In the lipid-lowering drug research, we found that cordycepin, a compound with different structural type with statins, exhibited such activity. The function of cordycepin was then patented. The relationship of the structure and activity, and the reaction mechanism (AMPK activator) of cordycepin and its analogues were investigated. A novel lipid-lowering molecule WS070117 with the independent intellectual property was developed. This novel drug research has entered the pre-clinical stage.
5. In the anti-microtubule drug research, a strategy of increasing the affinity between taxane and microtubule to antagonize the efflux effect of P-gp was proposed. The patented compound Aziditaxel (LX2-32C) has been proved to be a more potent cytotoxic agent against drug-resistant tumor as compared to paclitaxel. This candidate drug has also entered the pre-clinical stage.