Optimization of the l-tyrosine metabolic pathway in by analyzing -coumaric acid production.

Yuanzi Li, Jiwei Mao, Xiaofei Song, Yuzhen Wu, Miao Cai, Hesuiyuan Wang, Quanli Liu, Xiuming Zhang, Yanling Bai, Haijin Xu, Mingqiang Qiao
Author Information
  1. Yuanzi Li: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China.
  2. Jiwei Mao: Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Gothenburg, Sweden.
  3. Xiaofei Song: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China.
  4. Yuzhen Wu: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China.
  5. Miao Cai: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China.
  6. Hesuiyuan Wang: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China.
  7. Quanli Liu: Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Gothenburg, Sweden.
  8. Xiuming Zhang: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China.
  9. Yanling Bai: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China.
  10. Haijin Xu: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China. ORCID
  11. Mingqiang Qiao: The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071 People's Republic of China. ORCID

Abstract

In this study, we applied a series of genetic modifications to wild-type strain BY4741 to address the bottlenecks in the l-tyrosine pathway. A tyrosine ammonia-lyase (TAL) gene from , which can catalyze conversion of l-tyrosine into -coumaric acid, was overexpressed to facilitate the analysis of l-tyrosine and test the strain's capability to synthesize heterologous derivatives. First, we enhanced the supply of precursors by overexpressing transaldolase gene , enolase II gene , and pentafunctional enzyme gene resulting in a 1.55-fold increase in -coumaric acid production. Second, feedback inhibition of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase and chorismate mutase was relieved by overexpressing the mutated feedback-resistant and , and a 3.61-fold improvement of -coumaric acid production was obtained. Finally, formation of byproducts was decreased by deleting pyruvate decarboxylase gene and phenylpyruvate decarboxylase gene , and -coumaric acid production was increased 2.52-fold. The best producer-when , , , , , and were overexpressed, and and were deleted-increased -coumaric acid production by 14.08-fold (from 1.4 to 19.71 mg L). Our study provided a valuable insight into the optimization of l-tyrosine metabolic pathway.

Keywords

References

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