（1）DNA磷硫酰化修饰的生物学；

（2）微生物天然产物生物合成的酶学和化学生物学；

（3）应用于生物催化的新酶发现和工程化。

[1]      Kellner S, DeMott MS, Cheng CP, Russell BS, Cao B, You D, Dedon PC*. Oxidation of phosphorothioate DNA modifications leads to lethal genomic instability. Nat Chem Biol. 2017, 13(8): 888-94.

[2]      Zheng X, Cheng Q, Yao F, Wang X, Kong L, Cao B, Xu M, Lin S, Deng Z, Chooi YH*, You D*. Biosynthesis of the pyrrolidine protein synthesis inhibitor anisomycin involves novel gene ensemble and cryptic biosynthetic steps. Proc Natl Acad Sci U S A. 2017,114(16):4135-40. (Faculty of 1000专文评述)

[3]      Kong L, Zhang W, Chooi YH, Wang L, Cao B, Deng Z, Chu Y, You D*. A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation. Cell Chem Biol. 2016, 23(4):508-16 (Cell子刊).

[4]      Zheng T, Jiang P, Cao B, Cheng Q, Kong L, Zheng X, Hu Q*, You D*. DndEi exhibits helicase activity essential for DNA phosphorothioate modification and ATPase activity strongly stimulated by DNA substrate with a GAAC/GTTC motif. J Biol Chem. 2016, 291(3):1492-500. 

[5]      Cao B, Zheng X, Cheng Q, Yao F, Zheng T, Babu IR, Zhou H, Dedon PC, You D*. In vitro analysis of phosphorothioate modification of DNA reveals substrate recognition by a multiprotein complex. Sci Rep. 2015, 5: 12513.

[6]      Cheng Q, Cao B, Yao F, Li J, Deng Z, You D*. Regulation of DNA phosphorothioate modifications by the transcriptional regulator DptB in Salmonella. Mol Microbiol. 2015, 97(6): 1186-94.

[7]      Cao B, Cheng Q, Gu C, Yao F, DeMott MS, Zheng X, Deng Z, Dedon PC, You D*. Pathological phenotypes and in vivo DNA cleavage by unrestrained activity of a phosphorothioate-based restriction system in Salmonella. Mol Microbiol. 2014, 93(4):776-85.

[8]      Cao B, Chen C, DeMott MS, Cheng Q, Clark TA, Xiong X, Zheng X, Butty V, Levine SS, Yuan G, Boitano M, Luong K, Song Y, Zhou X, Deng Z, Turner SW, Korlach J, You D*, Wang L*, Chen S*, Dedon PC. Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences. Nat Commun. 2014, 5: 3951.

[9]      Zhu T, Cheng X, Liu Y, Deng Z, You D*. Deciphering and engineering of the final step halogenase for improved chlortetracycline biosynthesis in industrial Streptomyces aureofaciens. Metab Eng. 2013, 19:69-78.

[10]  Zhang C, Kong L, Liu Q, Lei X, Zhu T, Yin J, Lin B, Deng Z, You D*. In vitro characterization of echinomycin biosynthesis: formation and hydroxylation of L-tryptophanyl-S-enzyme and oxidation of (2S,3S) β-hydroxytryptophan. PLoS One 2013, 8 (2): e56772.

[11]  Lei X, Kong L, Zhang C, Liu Q, Yao F, Zhang W, Deng Z, You D*. In vivo investigation of the substrate recognition capability and activity affecting amino acid residues of glycosyltransferase FscMI in biosynthesis of candicidin. Mol Biosyst. 2013, 9 (3): 422-30.

[12]  Cao B, Yao F, Zheng X, Cui D, Shao Y, Zhu C, Deng Z, You D*. Genome mining of the biosynthetic gene cluster of the polyene macrolide antibiotic tetramycin and characterization of a P450 monooxygenase involved in the hydroxylation of the tetramycin B polyol segment. Chembiochem 2012, 13(15):2234-42.

[13]  Zhang W, Wang L, Kong L, Wang T, Chu Y, Deng Z, You D*. Unveiling the post-PKS redox tailoring steps in biosynthesis of the type II polyketide antitumor antibiotic xantholipin. Chem Biol. 2012, 19(3):422-32 (Cell子刊).

[14]  Liu Q, Yao F, Chooi Y, Kang Q, Xu W, Li Y, Shao Y, Shi Y, Deng Z, Tang Y*, You D*. Elucidation of piericidin A1 biosynthetic locus revealed a thioesterase-dependent mechanism of α-pyridone ring formation. Chem Biol. 2012, 19(2):243-53 (Cell子刊).

 [15]Wang T, Bai L, Zhu D, Lei X, Liu G, Deng Z, You D*. Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes. Enzyme Microb Technol. 2012, 50: 5-9. (Faculty of 1000专文评述)

 
主要从事微生物天然产物生物合成和DNA磷硫酰化修饰研究，关注具有杂环化学结构和显著生物活性的微生物天然产物茴香霉素、黄脂菌素、棘霉素、杀粉蝶菌素和金霉素的生物合成酶学机制及DNA骨架磷硫酰化修饰的生物学研究。近十年在两个研究方向做出以下学术贡献：揭示了杂环天然产物药效基团吡咯烷、呫吨酮、喹喔啉环和α-吡啶酮的生物合成酶学机制，提出了多个新型天然产物杂环结构的酶催化模型，首次发现天然产物生物合成中隐藏糖基化反应和脱甲氧基反应。与合作者创新了抗生素药物高产改良的共性技术，实现了抗菌药物克念菌素和金霉素产量的大幅提高。发现了DNA磷硫酰化依赖的新型修饰限制系统，破解了DNA磷硫酰化修饰的基因组分布规律和调控机制，揭示了磷硫酰化修饰酶复合体的功能。