Pentostatin is the first-line drug approved by the US Food and Drug Administration for the treatment of leukemia. Vidarabine is widely used in clinical treatment to diseases caused by herpes virus, cytomegalovirus and so on. Both of these drugs are accompanied by the same Streptomyces, however, the biosynthetic mechanism underlying has been long in the dark. until WHU scholars brought it to the surface for the first time recently.
The team of academician Deng Zixin , the research group of Associate Professor Chen Wenqing, Huadong Pharmaceutical Group and Professor Li Yongquan of Zhejiang University jointly achieved the clone and synthesis of two drug gene clusters, and this is a research outcome of important economic and clinical application value. The molecular of biosynthesis revealed for the first time a unique mechanism in nature—"one set of gene cluster for two medicines", which means the two accompanied each other and the synthesized Pentostatin protects Vidarabine from deamination. This research not only provides a theoretical basis for the use of biosynthetic strategy to achieve yield improvement and structural innovation, but also presents a new shortcut for other natural drug discovery and innovation through the study on the candidate gene.
On February 16th, the study was published in one of the Cell publication series—Cell Chemical Biology and has applied for a national invention patent. The co-authors of the paper are doctoral student Wu Pan, master student Wan Dan and Xu Gudan while the corresponding author is Chen Wenqing.
This research finding, as is reported, is another new achievement of their systematic and original research result in the field of nucleoside drugs after the last breakthrough in polyoxin biosynthetic studies. It further reinforced the leading role of China in the research field of nucleoside antibiotics drugs in recent years. In addition, the research group has also carried out a comprehensive strategic cooperation with the related enterprises in the production of Phytostatin and gentamicin molecular breeding. This is expected to stimulate the industrialization of related microbial drugs in our country .
Deng Zixin team has long been committed to the metabolic engineering and synthetic biology research of important microbial drugs. The last few years have witnessed their remarkable and prominent breakthroughs in the field of microbial drug biosynthesis and biosynthetic research. They have gained increasing international influence and are widely recognized by the international academic community.
The website for their paper:
(Rewritten by Hou Siliang, edited by Liu Jiachen, Shen Yuxi & Hu Sijia)