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Engineering Biology to Construct Microbial Chassis for the Production of Difficult-to-Express Proteins

by Kangsan Kim 1,2, Donghui Choe 1,2, Dae-Hee Lee 3 and Byung-Kwan Cho 1,2,4,*
1
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
2
KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
3
Synthetic Biology & Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
4
Intelligent Synthetic Biology Center, Daejeon 34141, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 990; https://doi.org/10.3390/ijms21030990
Received: 6 December 2019 / Revised: 28 January 2020 / Accepted: 31 January 2020 / Published: 2 February 2020
A large proportion of the recombinant proteins manufactured today rely on microbe-based expression systems owing to their relatively simple and cost-effective production schemes. However, several issues in microbial protein expression, including formation of insoluble aggregates, low protein yield, and cell death are still highly recursive and tricky to optimize. These obstacles are usually rooted in the metabolic capacity of the expression host, limitation of cellular translational machineries, or genetic instability. To this end, several microbial strains having precisely designed genomes have been suggested as a way around the recurrent problems in recombinant protein expression. Already, a growing number of prokaryotic chassis strains have been genome-streamlined to attain superior cellular fitness, recombinant protein yield, and stability of the exogenous expression pathways. In this review, we outline challenges associated with heterologous protein expression, some examples of microbial chassis engineered for the production of recombinant proteins, and emerging tools to optimize the expression of heterologous proteins. In particular, we discuss the synthetic biology approaches to design and build and test genome-reduced microbial chassis that carry desirable characteristics for heterologous protein expression. View Full-Text
Keywords: heterologous protein expression; difficult-to-express proteins; synthetic biology; systems biology; genome reduction; genome synthesis. heterologous protein expression; difficult-to-express proteins; synthetic biology; systems biology; genome reduction; genome synthesis.
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Kim, K.; Choe, D.; Lee, D.-H.; Cho, B.-K. Engineering Biology to Construct Microbial Chassis for the Production of Difficult-to-Express Proteins. Int. J. Mol. Sci. 2020, 21, 990.

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