Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway |
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| Institution: | 1. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;2. Beijing Key Laboratory of Plant Resources Research and Development, Beijing Technology and Business University, Beijing 100048, China;3. School of Chemistry and Biotechnology, Yunnan Minzu University, Kunming 650500, China;4. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;5. University of Chinese Academy of Sciences, Beijing 100049, China;1. Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA;2. Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, College of Bioengineering, Jimei University, 43 Yindou Road, Xiamen, Fujian 361021, China;1. State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China;2. Department of Biotechnology, Beijing Polytechnic, Beijing 100029, China;3. BioChemical Engineering Program, College of Engineering, University of Georgia, Athens, GA 30602, USA |
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| Abstract: | Salvianic acid A, a valuable derivative from L-tyrosine biosynthetic pathway of the herbal plant Salvia miltiorrhiza, is well known for its antioxidant activities and efficacious therapeutic potential on cardiovascular diseases. Salvianic acid A was traditionally isolated from plant root or synthesized by chemical methods, both of which had low efficiency. Herein, we developed an unprecedented artificial biosynthetic pathway of salvianic acid A in E. coli, enabling its production from glucose directly. In this pathway, 4-hydroxyphenylpyruvate was converted to salvianic acid A via D-lactate dehydrogenase (encoding by d-ldh from Lactobacillus pentosus) and hydroxylase complex (encoding by hpaBC from E. coli). Furthermore, we optimized the pathway by a modular engineering approach and deleting genes involved in the regulatory and competing pathways. The metabolically engineered E. coli strain achieved high productivity of salvianic acid A (7.1 g/L) with a yield of 0.47 mol/mol glucose. |
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| Keywords: | Salvianic acid A Metabolic engineering D-lactate dehydrogenase |
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