Director
Zixin Deng was born in Hubei, China. He received his BSc in microbiology at Huazhong Agricultural University in 1982. He completed his PhD under the supervision of Professor David A. Hopwood FRS and Dr Tobias Kieser (at the John Innes Center and the University of East Anglia, Norwich, UK) on the genetics of Streptomyces. He returned to Huazhong Agricultural University in June, 1988 to start a lectureship (1988 –1991), and has been appointed as a Professor since 1992. He moved to Shanghai Jiao Tong University in 2000 as the Vice Director at the Bio-X Life Science Research Center. Currently he is the Director of the Laboratory of Microbial Metabolism, Ministry of Education, and the Dean of the School of Life Science and Biotechnology. Research interests involve studies on DNA modifications, microbial metabolic pathways and pathway engineering related to natural product discovery and cell metabolism.
Research interests
(1) DNA sulfur modification
It began with an easily overlooked DNA degradation (Dnd) phenomenon during electrophoresis and eventually led to the discovery of an unprecedented DNA sulfur modification governed by five dnd genes. This unusual DNA modification, called phosphorothioation, is the first physiological modification identified on the DNA backbone, in which the non-bridging oxygen is replaced by sulfur in a sequence-selective and stereo-specific manner. Homologous dnd gene clusters have been identified in diverse and distantly related bacteria and thus have drawn immediate attention of the entire microbial scientific community. Chemical, genetic, enzymatic, bio-informatical and analytical aspects of this novel post-replicative DNA modification have been performed. The physiological functions of the DNA phosphorothioate modification in bacteria are comprehensively under investigation.
(2) Biosynthesis and engineering of microbial secondary metabolites
Our research activities include studies on antibiotic biosynthetic pathways and metabolic engineering in actinomycetes. The major original compounds under studies include anti-fungal aminocyclitol validamycin, insecticidal polyether ionophore nanchangmycin, anti-fungal heptaene macrolide candicidin, anti-parasitic macrolide meilingmycin, anti-tumor PKS-NRPS hybrid oxzolomycin, anti-fungal nucleoside peptide polyoxins and mildiomycin etc., all of which are of medicinal, agricultural and veterinary importance. Firstly, strategies for screening for potential clusters have been developed. Secondly, strategies are optimized for engineered over-production of important antibiotics and their most active components, which comprise heterologous expression of antibiotic gene clusters, expression of genes from other primary/secondary metabolic pathways with optimized codon usage, elimination of substrate competiting PKS gene clusters, and accumulation of most active components through domain silencing, etc. Thirdly, design of novel antibiotic derivatives is achieved through mutational biosynthesis, targeted domain/module inactivation or re-activation, combinatorial biosynthesis, and engineered pathway extension.
Selected publications
1. 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.
2. Xu F, Kong D, He X, Zhang Z, Han M, Xie X, Wang P, Cheng H, Tao M, Zhang L, Deng Z, Lin S*. Characterization of streptonigrin biosynthesis reveals a cryptic carboxyl methylation and an unusual oxidative cleavage of a N-C bond. J Am Chem Soc, 2013, 135(5):1739-1748.
3. Zou Y, Fang Q, Yin H, Liang Z, Kong D, Bai L, Deng Z, Lin S*. Stereospecific biosynthesis of β-methyl tryptophan from L-tryptophan features a stereochemical switch. Angew Chem Int Ed, 2013, 52, 12951-12955.
4. Xie X, Liang J, Pu T, Xu F, Yao F, Yang Y, Zhao YL, You D, Zhou X, Deng Z*, Wang Z*. Phosphorothioate DNA as an antioxidant in bacteria.Nucleic Acids Res, 2012, 40(18):9115-24.
5. Zhai L, Lin S, Qu D, Hong X, Bai L, Chen W*, Deng Z*. Engineering of an industrial polyoxin producer for the rational production of hybrid peptidyl nucleoside antibiotics. Metab Eng, 2012, 14(4):388-93.
6. Liu G, Ou HY, Wang T, Li L, Tan H, Zhou X, Rajakumar K, Deng Z*, He X*. Cleavage of phosphorothioated DNA and methylated DNA by the type IV restriction endonuclease ScoMcrA. PLoS Genet, 2010, 6(12):e1001253.
7. Wang L, Chen S, Xu T, Taghizadeh K, Wishnok JS, Zhou X, You D, Deng Z*, Dedon PC*. Phosphorothioation of DNA in bacteria by dndgenes. Nat Chem Biol, 2007, 3(11):709-10.
8. Deng Z, Bai L. Antibiotic biosynthetic pathways and pathway engineering—a growing research field in China. Nat Prod Rep, 2006, 23(5):811-27.
9. Zhou X, He X, Liang J, Li A, Xu T, Kieser T, Helmann JD, Deng Z*. A novel DNA modification by sulphur. Mol Microbiol, 2005, 57(5):1428-38.