Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects

  title={Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects},
  author={Yanfeng Liu and Hyun-dong Shin and Jianghua Li and Long Liu},
  journal={Applied Microbiology and Biotechnology},
Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution… 

Pathway Design, Engineering, and Optimization.

This chapter will review the computational algorithms and experimental tools used to design efficient metabolic routes, and construct and optimize biochemical pathways to produce chemicals of high interest.


The core metabolic model was constructed from an initial draft metabolic reconstruction including 74 reactions and 68 metabolites that provides insights for a better understanding of K. hansenii metabolic pathways and can facilitate system-level metabolic analysis as well as developments for improving BNC production.

Integration and Validation of the Genome-Scale Metabolic Models of Pichia pastoris: A Comprehensive Update of Protein Glycosylation Pathways, Lipid and Energy Metabolism

In order to provide an updated and more comprehensive GEM for P. pastoris, a consensus model integrating and merging all three existing models is reconstructed and validated, and the resulting iMT1026 model includes a new description of some metabolic processes.

Metabolic engineering of Yarrowia lipolytica for industrial applications.

Transcriptomics‐based strain optimization tool for designing secondary metabolite overproducing strains of Streptomyces coelicolor

A transcriptomics‐based strain optimization tool (tSOT) is developed in order to overcome limitations by integrating transcriptomic data into GEM and successfully demonstrated its applicability to secondary metabolites overproduction by designing actinorhodin (ACT), a polyketide antibiotic, overproducing strain of S. coelicolor.



Protein design in systems metabolic engineering for industrial strain development

The current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways are reviewed, and the challenges of this subfield are highlighted within the context of systems metabolic engineering.

Synthetic biology and metabolic engineering.

This paper reviews the origins of the two fields and advances two distinct paradigms for each: that of unit operations for metabolic engineering and electronic circuits for synthetic biology.

Systems metabolic engineering of microorganisms for natural and non-natural chemicals.

The general strategies of systems metabolic engineering are discussed and examples of its application are offered and insights are offered as to when and how each of the different strategies should be used.

Multivariate modular metabolic engineering for pathway and strain optimization.

Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks.

Synthetic protein scaffolds provide modular control over metabolic flux

Engineered metabolic pathways constructed from enzymes heterologous to the production host often suffer from flux imbalances, as they typically lack the regulatory mechanisms characteristic of

Optimization of a blueprint for in vitro glycolysis by metabolic real-time analysis.

The development and application of a new in vitro real-time analysis method for the comprehensive investigation and rational programming of enzyme networks for synthetic tasks and drastically accelerates rational optimization of synthetic multienzyme networks.

Genome-scale metabolic model in guiding metabolic engineering of microbial improvement

This review highlights the application of GSMM in guiding microbial improvements focusing on a systematic strategy and its achievements in different industrial fields, including food and nutrients, biopharmaceuticals, biopolymers, microbial biofuel, and bioremediation.

Improving fatty acids production by engineering dynamic pathway regulation and metabolic control

A genetically encoded metabolic switch that enables dynamic regulation of fatty acids (FA) biosynthesis in Escherichia coli was reported, able to dynamically compensate the critical enzymes involved in the supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward FA biosynthesis.