Professor Sun Yuhui’s research group from the team of CAS member Deng Zixin has made important progress with research on active natural products against resistant bacteria. The result has been published online on ACS Chemical Biology, periodical of American Chemical Society.
The thesis, titled with Functional Analysis of Cytochrome P450s Involved in Streptovaricin Biosynthesis and Generation of Anti-MRSA Analogues, is co-written by team member Doctor Liu Zhenyuan as the first author and Professor Sun Yuhui asthe corresponding author.
Due to antibiotics abuse, pathogenic bacteria with high pathogenicity and multi-drug resistance (MDR) such as Methicillin-resistant Staphylococcus aureus or MRSAT have emerged as a huge threat to public health. In order to solve the problem, the research team has spared no efforts to develop new drug molecule against those superbugs.
Researchers got an isolated Streptomyces spectabilis CCTCC M2017417 from the soil of Luojia Hill. They find that its fermentation products had strong anti-MRSA activity. After bio-assay-guided investigation, team members identified the potent compounds as Streptovaricins, a kind of ansamycins.
Through molecular genetics, chemicobiology, and bioinformatics approaches, scientists explored thoroughly the mechanism of streptovaricin bio-synthesis. It’s in this process that researchers find, from biosynthetic gene cluster, several P450 genes which are responsible for redox. Also, they accumulated and identified 10 streptovaricin analogues (4 of which were newly found compound) through targeted genetic operation. Meanwhile, the team utilized both standard MRSA strain and clinically isolated strain to clarify how different structures and groups contributed to activity. The reveal of these vital structure-activity relationships obviously provides solid theoretical foundation for targeted and rational modification on streptovaricin and the production of highly effective anti-MRSA drug.
Members of Deng Zixin research team have long been committed to the study of microorganism’s natural products bio-synthesis and its synthetic biology with constant innovative research results on issues including drug discovery, modification, and invention.
The research group led by Professor Sun Yuhui has discovered a new growing point on the field of natural products and set a new model for research on active natural products. The research is funded by Open Foundation of State Key Laboratory of Microbial Metabolism, National Natural Science Foundation for Young Scientists of China, China Postdoctoral Science Foundation, and other foundation projects.
Rewritten by Li Xin
Edited by Shen Yuxi, Hu Sijia
