Research Field: Chemical Biology
The research field of my lab spans a broad range of chemical biology, structure biology, epigenetics and drug discovery. We are interested in studying the dynamic catalytic and regulation mechanisms of chemical modifications on biological macromolecules involved in Fatty acid biosynthesis, Nucleoside biosynthesis, and DNA/RNA methylation/demethylation pathways. These processes are vital for all living cells, and the biofunctions of enzymes involved in these processes are restrictively regulated spatio-temporally through chemical modifications. Our researches focus on elucidating the mechanisms of the key enzymes in adding, reading, catalytic changing and removing the chemical modifications on the biological macromolecules, as well as the subsequent corresponding biological effects. We are also establishing efficient high throughput drug screening systems for novel leading drug compounds discovery against these potential drug targets. So far, our lab has published several research articles on Nature Chemical Biology, Nature Communications, Cell Research, PNAS, Chemical Science, Elife, etc, and obtained 2 national patents and applied for a domestic patent. Our works are supported by numerous grants such as the National Science Fund for Excellent Young Scholars, the Major Research Plan and General Program Research Plan of National Natural Science Foundation of China, Shanghai Shuguang Scholar program, Oriental Scholar of Shanghai College, and Shanghai Biomedical science and technology innovation program, etc.
Scientific Research Projects
National Science Fund for Excellent Young Scholars, 21722802;
The Major Research Plan of National Natural Science Foundation of China, 91853118;
The General Program Research Plan of National Natural Science Foundation of China, 22077081, 21572133;
Shanghai Shuguang Scholar program,20SG16;
Oriental Scholar of Shanghai College;
Shanghai Biomedical science and technology innovation program, 22S11900600, 20S11900300;
Y.J. Mu, L. Zhang, J.Y. Hu, J.S. Zhou, H.W. Lin, C. He, H.Z. Chen, and L. Zhang. A fungal dioxygenase CcTet serves as a eukaryotic 6mA demethylase on duplex DNA. Nat. Chem. Biol., 2022, in press.
P. Zhang#, L. Zhang#,*, Z.Y. Hou, H.W. Lin, H. Gao*, and L. Zhang*. Structural basis for the substrate recognition mechanism of ATP-sulfurylase domain of human PAPS synthase 2. Biochem. Biophys. Res. Commun., 2021, 586, 1.
J.S. Zhou#, L. Zhang#, L.P. Zeng#, L. Yu#, Y.Y. Duan#, S.Q. Shen#, J.Y. Hu, P. Zhang, W.Y. Song, X.X. Ruan, J. Jiang, Y.N. Zhang, L. Zhou, J. Jia, X.D. Hang, C.L Tian, H.Z. Chen*, J.E. Cronan*, H.K. Bi*, L. Zhang*. Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis. Nat. Commun., 2021, 12, 6932.
G.K. Chen#, J.S. Zhou#, Y.L. Zuo, W.P. Huo, J. Peng, M. Li, Y.N. Zhang, T.T. Wang, L. Zhang, L. Zhang*, H.H. Liang*. Structural basis for diguanylate cyclase activation by its binding partner in Pseudomonas aeruginosa. Elife. 2021, 10, e67289.
S.H. Xiao#, S.Q. Guo, J. Han, Y.L. Sun, M.C. Wang, Y.T. Chen, X.Y. Fang, F. Yang, Y.J. Mu, L. Zhang, Y.L. Ding, N.X. Zhang, H.L. Jiang, K.X. Chen, K.H. Zhao, C. Luo, S.J. Chen*. High-Throughput-Methyl-Reading (HTMR) assay: a solution based on nucleotide methyl-binding proteins enables large-scale screening for DNA/RNA methyltransferases and demethylases. Nucleic Acids Res., 2021, in press.
R.Y. Shang, J. Cui, J.X. Li, X.X. Miao, L. Zhang, D.D. Xie, L. Zhang, H.W. Lin, W.H. Jiao. Nigerin and ochracenes J−L, new sesquiterpenoids from the marine sponge symbiotic fungus Aspergillus niger. Tetrahedron, 2021, in press.
J.S. Zhou, L. Zhang, L. Zhang*. Advances on Mechanism and Drug Discovery of Type-II Fatty Acid Biosynthesis Pathway. Acta Chimica Sinia, 2020, 78, 1383.
T. R. Fu#, L. P. Liu#, Q. L. Yang#, Y. X. Wang, P. Xu, L. Zhang, S. E. Liu, Q. Dai, Q. J. Ji, G. L. Xu, C. He, C. Luo* and L. Zhang*. Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine. Chem. Sci. 2019, 10, 7407.
S. Q. Shen#, X. D Hang#, J. J. Zhuang#, L. Zhang*, H. K. Bi* and L. Zhang*. A back-door Phenylalanine coordinates the stepwise hexameric loading of acyl carrier protein by the fatty acid biosynthesis enzyme β-hydroxyacyl-acyl carrier protein dehydratase (FabZ). Int. J. Biol. Macromol. 2019, 128, 5.
X. Zhang#, L. H. Wei#, Y. X. Wang#, Y. Xiao#, J. Liu, W. Zhang, N. Yan, G. B. Amu, X. J. Tang, L. Zhang* and G. F. Jia*. Structural insights into FTO's catalytic mechanism for the demethylation of multiple RNA substrates. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 2919.
L. Zhang, J. F. Xiao, J. R. Xu, T. R. Fu, Z. W. Cao, L. Zhu, H. Z. Chen, X. Shen, H. L. Jiang and L. Zhang*. Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis. Cell Res. 2016, 26, 1330.
L. Zhang#, W. Z. Chen#, L. M. Iyer, J. Hu, G. Wang, Y. Fu, M. Yu, Q. Dai, L. Aravind and C. He. A TET homologue protein from Coprinopsis cinerea (CcTET) that biochemically converts 5-Methylcytosine to 5-Hydroxymethylcytosine, 5-Formylcytosine, and 5-Carboxylcytosine. J. Am. Chem. Soc. 2014, 136, 4801.
L. Zhang#, K. E. Szulwach#, G. C. Hon#, C. X. Song, B. Park, M. Yu, X. Y. Lu, Q. Dai, X. Wang, C. R. Street, H. P. Tan, J. H. Min, B. Ren, P. Jin, C. He. Tet-mediated covalent labelling of 5-methylcytosine for its genome-wide detection and sequencing. Nat. Commun. 2013, 4, 1517.
L. Zhang, X. Y. Lu, J. Y. Lu, H. H. Liang, Q. Dai, G. L. Xu, C. Luo, H. L. Jiang, C. He. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat. Chem. Biol. 2012, 8, 328.
C. He, L. Zhang, C. X. Song, M. Yu. Composition and Methods Related to Modification of 5-methylcytosine (5mC). 2012, Publication number: WO WO2012138973 A3.
K. Jonas, C. He, T. A. Clark, L. Zhang, X. Y. Lu. Identification of 5-methyl-c in nucleic acid templates. 2013, Publication number: WO2013163207 A1.