Ming Jiang

Molecular Microbiology Laboratory, Shanghai Jiaotong University

Summary of my work

Natural products are valuable sources of bioactive molecules, such as nutraceuticals and pharmaceuticals. My research is focused on natural product biosynthesis. In particular, we are conducting biosynthetic studies of antibacterial and antitumor natural products. Our goal is to clone the intact biosynthetic gene cluster, understand the biosynthetic pathways, and elucidate the biochemical and structural basis of the enzymatic reactions encoded in the complex biosynthetic pathways. The knowledges obtained from these studies are then used for engineering biosynthesis of modified natural products, through combinatorial biosynthesis and pathway engineering. We also conduct heterologous production of natural products using a surrogate microbial host. This approach provides a convenient platform for both production and discovery of natural products, especially for those produced by microbes that are difficult to culture or even do not grow in normal lab conditions. We have successfully produced both type I and type II polyketides heterologously in a widely used host E. coli, which offers great convenience in the biosynthetic engineering efforts for polyketide natural products.

During my stay at Cornell, I was in Professor Delisa’s research group, where I mainly focused on cell free biosynthesis of natural products including glycosylation. Different from the traditional production of natural products, crude extracts from specific cells are used in cell-free systems. Cell-free biosynthetic systems provide an easy-to-use platform for both biosynthetic studies and production of natural products. It will become a complementary tool for current natural product producing systems.

Impacts in China

Natural product research in China has made a great progress in recent years. The number of new natural products discovered in China increases exponentially in last 30 years. The biosynthetic studies of natural products help to understand and engineer the biosynthesis of natural products. Antibiotic fermentation industry is of great importance in China. My research is focused on the natural product biosynthesis. Biosynthetic studies of relevant natural products help to increase the efficiency of industrial fermentation and provide enzymatic tools that could be used for engineered biosynthesis of unnatural natural products with potentially better bioactivity.

Publications:

1. Hua K, Liu X, Zhao Y, Gao Y, Pan L, Zhang H, Deng Z, Jiang M. Offloading Role of a Discrete Thioesterase in Type II Polyketide Biosynthesis. mBio.2020, 11(5): e01334-20.
2. Liu X, Hua K, Liu D, Wu ZL, Wang Y, Zhang H, Deng Z, Pfeifer BA, Jiang M. Heterologous Biosynthesis of Type II Polyketide Products Using E. coli. ACS Chem Biol. 2020, 15(5):1177-1183.
3. Li Z, Lu Y, Wang X, Vekariaa A, Jiang M, Zhang H. Enhancing anthranilic acid biosynthesis using biosensor-assisted cell selection and in situ product removal. Biochemical Engineering Journal 2020, 162: 107722.
4. Xu G, Kong L, Gong R, Xu L, Gao Y, Jiang M, Cai YS, Hong K, Hu Y, Liu P, Deng Z, Price NPJ, Chen W. Coordinated Biosynthesis of the Purine Nucleoside Antibiotics Aristeromycin and Coformycin in Actinomycetes. Appl. Environ. Microb. 2018, 84(22): e01860-18.
5. Liu X, Liu D, Xu M, Tao M, Bai L, Deng Z, Pfeifer BA, Jiang, M, Reconstitution of kinamycin biosynthesis within the heterologous host Streptomyces albus J1074, J Nat Prod., 2018, 81(1): 72~77.
6. Jiang M*, Zhang H, Engineering the shikimate pathway for biosynthesis of molecules with pharmaceutical activities in E. coli. Curr Opin Biotechnol. 2016, 42:1-6.
7. Gao G, Liu X, Xu M, Wang Y, Zhang F, Xu L, Lv J, Long Q, Kang Q, Ou HY, Wang Y, Rohr J, Deng Z, Jiang M*, Lin S*, Tao M*. Formation of an angular aromatic polyketide from a linear anthrene precursor via oxidative rearrangement. Cell Chem Biol. 2017, 24(7):881-891.
8. Lu C, Zhang X, Jiang M, Bai L. Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus. Metab Eng. 2016, 35:129-137.
9. Liao L., Chen R., Jiang M, Tian X, Liu H., Yu Y., Fan C., Chen B., Bioprospecting potential of halogenases from Arctic marine actinomycetes. BMC Microbiol. 2016, 16:34. doi: 10.
10. Yu G, Li L, Liu X, Liu G, Deng Z, Zabriskie MT, Jiang M*, He X*, The standalone aminopeptidase PepN catalyzes the maturation of blasticidin S from leucylblasticidin S. Sci Rep. 2015, 5:17641.
11. Jiang C, Qi Z, Kang Q, Liu J, Jiang M, Bai L. Formation of the Δ(18,19) double bond and bis(spiroacetal) in salinomycin is atypically catalyzed by SlnM, a methyltransferase-like enzyme. Angew Chem Int Ed Engl. 2015, 54(31):9097-100.
12. Jiang M; Zhang H.; Park SH.; Li Y; Pfeifer BA. Deoxysugar pathway interchange for erythromycin analogues heterologously produced through Escherichia coli. Metab Eng. 2013, 20:92-100.
13. Jiang M; Pfeifer BA. Metabolic and pathway engineering to influence native and altered erythromycin production through E. coli. Metab Eng. 2013, 19:42-49.
14. Jiang M, Fang L, Pfeifer BA. Improved heterologous erythromycin A production through expression plasmid re-design. Biotechnol Prog. 2013, 29(4):862-869.
15. Chen CK, Jones CH, Mistriotis P, Yu Y, Ma X, Ravikrishnan A, Jiang M, Andreadis ST, Pfeifer BA, Cheng C. Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing charge density for gene delivery. Biomaterials. 2013, 34(37):9688-9699.
16. Chen M, Ma X, Chen X, Jiang M, Song H, Guo Z. Identification of a hotdog fold thioesterase involved in the biosynthesis of menaquinone in Escherichia coli. J Bacteriol. 2013, 195(12):2768-2775.