Bulletin of Chinese Academy of Sciences (Chinese Version)


computational design; metabolic engineering; biosynthesis; dynamic regulation; metabolic network; synthetic biology

Document Type



One main objective of metabolic engineering is to rewire the metabolic network for efficient production of biochemicals. Due to the complexity of cellular metabolic networks, it is often not straightforward to identify the proper modification targets from thousands of metabolic genes. Therefore, a time-consuming trial & error process is often required for the successful development. Aided by computational modeling of large-scale metabolic networks, one can design optimal pathways for synthesis of objective products, reducing the uncertainty of development and thus accelerating the strain construction process. In this short text, we give brief introduction to metabolic engineering design methods from two aspects:how to modify an organism to produce new chemicals with higher yields, and how to improve the cellular adaptation to the changing process conditions by integrating gene circuits. The computer aided design approach together with automated genome edition technologies, will greatly enhance the efficiency of the construction of artificial cell factories.

First page


Last Page





Bulletin of Chinese Academy of Sciences


Thiele I, Palsson B O. A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc, 2010, 5(1):93-121.

Galanie S, Thodey K, Trenchard I J, et al. Complete biosynthesis of opioids in yeast. Science, 2015, 349(6252):1095-1100.

Zhang X, Tervo C J, Reed J L. Metabolic assessment of E. coli as a Biofactory for commercial products. Metab Eng, 2016, 35:64-74.

Chatsurachai S, Furusawa C, Shimizu H. An in silico platform for the design of heterologous pathways in nonnative metabolite production. BMC Bioinformatics, 2012, 13:93.

Hadadi N, Hafner J, Shajkofci A, et al. ATLAS of biochemistry:A repository of all possible biochemical reactions for synthetic biology and metabolic engineering studies. ACS Synth Biol, 2016, 5(10):1155-1166.

Tokic M, Hadadi N, Ataman M, et al. Discovery and evaluation of biosynthetic pathways for the production of five methyl ethyl ketone precursors. ACS Synth Biol, 2018, 7(8):1858-1873.

Orth J D, Thiele I, Palsson B O. What is flux balance analysis? Nat Biotechnol, 2010, 28(3):245-248.

McCloskey D, Palsson B O, Feist A M. Basic and applied uses of genome-scale metabolic network reconstructions of Escherichia coli. Mol Syst Biol, 2013, 9:661.

Lin Z, Zhang Y, Yuan Q, et al. Metabolic engineering of Escherichia coli for poly(3-hydroxybutyrate) production via threonine bypass. Microb Cell Fact, 2015, 14:185.

Bogorad I W, Lin T S, Liao J C. Synthetic non-oxidative glycolysis enables complete carbon conservation. Nature, 2013, 502(7473):693-697.

Yang X, Yuan Q, Zheng Y, et al. An engineered non-oxidative glycolysis pathway for acetone production in Escherichia coli. Biotechnol Lett, 2016, 38(8):1359-1365.

Zheng Y, Yuan Q, Yang X, et al. Engineering Escherichia coli for poly-(3-hydroxybutyrate) production guided by genome-scale metabolic network analysis. Enzyme Microb Technol, 2017, 106:60-66.

Meadows A L, Hawkins K M, Tsegaye Y, et al. Rewriting yeast central carbon metabolism for industrial isoprenoid production. Nature, 2016, 537(7622):694-697.

Wall M E, Hlavacek W S, Savageau M A. Design of gene circuits:lessons from bacteria. Nat Rev Genet, 2004, 5(1):34-42.

Zhang F, Keasling J. Biosensors and their applications in microbial metabolic engineering. Trends Microbiol, 2011, 19(7):323-329.

Xu P. Production of chemicals using dynamic control of metabolic fluxes. Curr Opin Biotechnol, 2017, 53:12-19.

Brockman I M, Prather K L. Dynamic metabolic engineering:New strategies for developing responsive cell factories. Biotechnol J, 2015, 10(9):1360-1369.

Brockman I M, Prather K L. Dynamic knockdown of E. coli central metabolism for redirecting fluxes of primary metabolites. Metab Eng, 2015, 28:104-113.

Mahr R, von Boeselager R F, Wiechert J, et al. Screening of an Escherichia coli promoter library for a phenylalanine biosensor. Appl Microbiol Biotechnol, 2016, 100(15):6739-6753.

Gupta A, Reizman I M, Reisch C R, et al. Dynamic regulation of metabolic flux in engineered bacteria using a pathway-independent quorum-sensing circuit. Nat Biotechnol, 2017, 35(3):273-279.