Bioswitches and robotics for systems metabolic engineering and synthetic biology of hyper microbial production strain

Conference Dates

July 14-18, 2019


Despite impressive progresses in systems metabolic engineering and synthetic biology, there are still several unsolved major challenges in their practical applications for developing effective metabolic pathways and microorganisms for biosynthesis: 1. identification of targets for advanced pathway engineering of productive strains, especially under industrially relevant and in vivo conditions; 2. effective means with proper dynamic range and sensitivity for dynamic and concerted control of metabolic pathways; 3. designed parts from synthetic biology often not work well within the host cells, especially for highly productive strains; 4. mathematical models of cellular processes often miss regulatory details inside cells and thus fail to guide biomolecular and cellular design. In this talk, I will illustrate our recent efforts to address some of these questions, especially for developing industrially relevant production strains with high yield and productivity (Ref. 1-5). After a short introduction, I will first present results on rational design of bioswitches (riboswitch and allosteric regulation) for dynamic control of metabolic pathways. Then, I will address the question how we can use host cells as parallel “robots” to identify targets and evaluate designed parts. Also recent work in developing a robotic system for algorithm-guided biomolecular design and optimization will be presented. The methods and techniques are successfully applied to develop highly productive strains for the biosynthesis of L-lysine, tryptophan and 5- aminolevulinic acid. References 1. J. Ren, L. Zhou, C. Wang, C. Lin, Z. Li and A.-P. Zeng (2018) An unnatural pathway for efficient 5- aminolevulinic acid biosynthesis with glycine from glyoxylate based on retrobiosynthetic design. ACS Synth. Biol. 7, 2750–2757 2. L. Chen, M. Chen, C. Ma, and A.-P. Zeng (2018) Discovery of feed-forward regulation in L-tryptophan biosynthesis and its use in metabolic engineering of E. coli for efficient tryptophan bioproduction. Met. Eng. 47, 434-444. 3. J. Mora-Villalobos and A.-P. Zeng (2018) Synthetic pathways and processes for effective production of 5-hydroxytryptophan and serotonin from glucose in Escherichia coli. J. Biol. Eng. 12 (1):3. 4. L. Song and A.-P. Zeng (2017) Engineering cells as robots for parallel and highly sensitive screening of biomolecules under in vivo conditions. Sci. Report, 7 (1), 15145. 5. L. Zhou and A.-P. Zeng (2015) Exploring Lysine Riboswitch for Metabolic Flux Control and Improvement of l-Lysine Synthesis in Corynebacterium glutamicum. ACS Synthetic Biology. 4:729-34

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