研究方向
以海洋微生物來源的藥物先導物為目標分子,從基因和蛋白水平揭示其生物合成途徑及其調控機制;在此基礎上,採用代謝工程方法與策略提高目標化合物的產量,並理性設計和創造出“非天然”的化合物。主要包括:
1、海洋藥物先導物生物合成研究;
2、海洋藥物先導物組合生物合成(Combinatorial biosynthesis)與代謝工程;
3、基於基因組採掘(Genome mining)的新型海洋藥物先導物的發現。
主要科研項目
1、自然科學基金委項目:“海洋芽孢桿菌B-9987中Macrolactins生物合成後修飾基因與調控基因的作用機制”(項目編號:31070072,2011年1月-2013年12月,項目負責人);
2、自然科學基金委項目:“南海紅樹林鏈黴菌sp. OUC6819中新型DKP-Terpenoid雜合抗生素Drimentine C的生物合成研究”(項目編號:31171201,2012年1月-2015年12月,項目負責人);
3、自然科學基金委項目:“海洋鏈黴菌中P450酶參與催化吲哚咔唑化合物形成的新穎分子機制”(項目編號:41506157,2016年1月-2018年12月,項目負責人);
4、自然科學基金委項目:“海洋遊絲鏈黴菌新穎隱性次級代謝基因簇的激活及其產物的定向發現”(項目編號:31570032,2016年1月-2019年12月,項目負責人);
5、國家科技部“863”項目:“深海微生物活性物質的挖掘及其利用技術”(2012AA092104),第2位,學術骨幹;
6、教育部“新世紀優秀人才”項目(NCET-09-0717,2010年1月-2012年12月,項目負責人);
7、中國海洋大學“英才工程”項目(項目負責人)。
近期SCI
1.Zhang Y.; Huang H.; Xu S.; Wang B.; Ju J.; Tan H.; Li W.*. Activation and enhancement of Fredericamycin A production in deepsea-derived Streptomyces somaliensisSCSIO ZH66 by using ribosome engineering and response surface methodology. Microb Cell Fact. 2015, DOI: 10.1186/s12934-015-0244-2.
2.Che Q. ; Li T. ; Liu X.; Yao T.; Li J.; Gu Q.; Li D.*, Li W.*; Zhu T*. Genome scanning inspired isolation of reedsmycins A-F, polyene-polyol macrolides from Streptomycessp. CHQ-64. RSC Adv. 2015, 5, 22777-22782.
3.Ding X.; Chen C.; Cui Q.; Li W.*; Feng Y. Resonance assignments of the periplasmic domain of a cellulose-sensing trans-membrane anti-sigma factor from Clostridium thermocellum. Bimol NMR Assign. 2015, DOI: 10.1007/s12104-015-9601-7.
4.Song X.; Wang X.; Tan Y.; Feng Y.; Li W.; Cui Q.High production of squalene using a newly isolated yeast-like strain Pseudozymasp. SD301. J. Agric. Food Chem.2015,DOI: 10.1021/acs.jafc.5b03539.
5.Qin W.; Liu Y.; Ren P.; Zhang J.; Li H.; Tian L.; Li W* .Uncovering a glycosyltransferase provides insights into the glycosylation step during macrolactins and bacillaenes biosynthesis. ChemBioChem, 2014,15(18), 2747-2753.
6.Liu Y.; Zheng H.; Qin W.; Zhan G.; Tian L; Li W* .Establishment of an efficient transformation protocol and its application in marine-derived Bacillusstrain. Sci. China Life Sci.2014, 57, 627-635.
7.Li T.; Du Y.; Cui Q.; Zhang J.; Zhu W.; Hong K.*; Li W* .Cloning, characterization and heterologous expression of the indolocarbazole biosynthetic gene cluster from marine-derived Streptomyces sanyensisFMA. Mar. Drugs2013, 11, 466-488.
8.Gao M.; Song X.; Feng Y.; Li W.; Cui Q. Isolation and characterization of Aurantiochytriumspecies: high docosahexaenoic acid (DHA) production by the newly isolated microalga, Aurantiochytriumsp. SD116. JOleoSci. 2013, 62(3), 143-151.
9.Cui G.; Hong W.; Zhang J.; Li W.; Feng Y.; Liu C.; Cui Q.Targeted gene engineering in Clostridium cellulolyticumH10 without methylation. J. Microbiol. Methods.2012, 89, 201-208.
10.Yang D.; Li W.; Huang S.; Shen B. Functional characterization of ttnIcompleting the tailoring steps for tautomycetin biosynthesis in Streptomyces griseochromogenes. Org. Lett.2012, 14(5), 1302-1305.
11.Luo Y.; Li W.; Ju J.; Yuan Q.; Peter N.R.; Hoffmann F.M.; Huang S.; Bugni T.S.; Rajski S.; Osada H.; Shen B. Functional characterization of TtnD and TtnF, unveiling new insights into tautomycetin biosynthesis. J. Am. Chem. Soc.2010, 132, 6663-6671.
12.Ju J.; Li W. ; Yuan Q.; Peters N.R.; Hoffmann F.M.; Rajski S.R.; Shen B. Functional characterization of ttmMunveils new tautomycin analogs and insight into tautomycin biosynthesis and activity. Org. Lett.2009, 11(7), 1639-1642.( Contributed equally).
13. Li W.; Luo Y.; Ju J.; Rajski S.R.; Osada H.; Shen B. Characterization of the tautomycetin biosynthetic gene cluster from Streptomyces griseochromogenes." J. Nat. Prod. 2009, 72, 450-459.
14.Lin S.; Geoffrey P.H.; Chen Y.; Li W; Shen B. Characterization of the SgcF epoxide hydrolase supporting an ( R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis. J. Am. Chem. Soc.2009, 131, 16410-16417.
15.Pinchot, S.N.; Adler, J.T.; Luo, Y.; Ju, J.; Li W; Shen, B; Kunnimalaiyaan, M.; Chen, H. Tautomycin suppresses growth and neuroendocrine hormone markers in carcinoid cells through activation of the Raf-1 pathway. Am. J. Surg.2009, 197(3), 313-319.
16. Li W .; Ju J.; Osada H.; Shen B. Characterization of the tautomycin biosynthetic gene cluster from Streptomyces spiroverticillatusunveiling new insights into dialkylmaleic anhydride and polyketide biosynthesis." J. Bio. Chem.2008, 283(42), 28607-28617.
授權專利:
李文利,秦文,劉揚,一種葡萄糖基轉移酶及其套用, 授權號:201310283702.0.