·     Synthetic biology is a new multidisciplinary and integratied biotechnology. Our lab focuses on synthetic biology for the production of natural and unnatural products.

·    Plant-derived polyphenolic metabolites, such as salvianic acid A (danshensu) and salvianolic acids, resveratrol, cucurmins and flavonoids (catalyzed by polyketide synthase III, PKS III) are used as medicines and nutraceuticals in pharmaceutical and food industries. By using modular engineering approach integrated into the chromosome and deleting genes involved in the regulatory and competing pathways, we have been established plasmid-free and inducer-free E. coli chassis for efficient production of aromatic compounds. The unprecedented artificial biosynthetic pathways of salvianic acid A and 4-hydroxymandelic acid were designed, constructed, and functionally tested. Those high-value chemicals would be efficiently produced with glucose or glucose-xylose mixture by fed-batch fermentation strategy. L-tyrosine platform is now available for production of other L-tyrosine derivatives with their biosynthetic pathways.

·    Antibiotics are important drugs and widely used in clinics to treat infections, cancers and varscular diseases. The antibiotic biosynthesis of Streptomyces is strictly regulated by transcription factors at global, pleiotropic, and or pathway-specific levels. Our another interest is to engineer streptomyces for improve the titer and purity of antibiotics.

·    Monensin, a polyether ionophore antibiotic produced by Streptomyces cinnamonensis, has been worldwide used as a growth promoting and coccidiostatic agent in the cattle and poultry breeding. In recent years, monensin showed the ability to induce cell apoptosis and inhibit proliferation of cancer cells. We identified three positive pathway-specific regulators (MonH, MonRI and MonRII) and their regulatory cascades by MonH followed by monRII and then MonRI. DasR and Crp were characterized as two galuble positive regulators in biosynthesis of monensin. Co-regulation of MonH, MonRI, and MonRII with DasR and/or Crp improved the production of monensin.

·     Lincomycin A, a major fermentation product of Streptomyces lincolnensis, shows efficacious therapeutic effect on infective diseases caused by Gram-positive bacteria. However, lincomycin B is also produced as impurity in the fermentation broth, which exhibits lower bioactivity and higher toxicity. For the first time, we identified lmbW of lincomycin biosynthetic pathway to encode a C-methyltransferase invovled in biosynthesis of lincomycin A. Co-overexpression of lmbW and metK in a engineered strain significantly enhanced the titer of lincomycin A and decreased lincomycin B.

• Natural Products and Traditional Chinese Medicines
• Pharmaceutical Biotechnology
• Synthetic biology

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• Liang Zhou.Chromosome engineering of Escherichia coli for constitutive production of salvianic acid A.Microbial Cell Fa....2017,16 :8
• Separation of salvianic acid A from the fermentation broth of engineered Escherichia coli using macroporous resins.Journal of Separa....2015,38 :2833–2840
• Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway.Metabolic Enginee....2013,19 :79-87
• Engineering Escherichia coli for production of 4-hydroxymandelic acid using glucose-xylose mixture.Microbial Cell Fa....2016,15 :90
• Characterization of three pathway-specific regulators for high production of monensin in Streptomyces cinnamonensis.Applied Microbiol....2017,101 (15):6083–6097
• DasR positively controls monensin production at two-level regulation in Streptomyces cinnamonensis.Journal of Indust....2016,43 (12):1681–1692
• Co-overexpression of lmbW and metK led to increased lincomycin A production and decreased byproduct lincomycin B content in an industrial strain of Streptomyces lincolnensis.Journal of Applie....2015,4 (1064-1074)
• Characterization of the radical scavenging and antioxidant activities of danshensu and salvianolic acid B.Food and Chemical....2008,46 (1):73-81
• Antioxidant activities of Salvia miltiorrhiza and Panaxnotoginseng.Food Chemistry.2006,99 :767-774