Systems strategies for developing industrial microbial strains
Top Cited Papers
- 8 October 2015
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 33 (10), 1061-1072
- https://doi.org/10.1038/nbt.3365
Abstract
Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenges have been the time-, cost- and labor-intensive processes of strain development owing to the difficulties in understanding complex interactions among the metabolic, gene regulatory and signaling networks at the cell level, which are collectively represented as overall system performance under industrial fermentation conditions. These challenges can be overcome by taking systems approaches through the use of state-of-the-art tools of systems biology, synthetic biology and evolutionary engineering in the context of industrial bioprocess. Major systems metabolic engineering achievements in recent years include microbial production of amino acids (L-valine, L-threonine, L-lysine and L-arginine), bulk chemicals (1,4-butanediol, 1,4-diaminobutane, 1,5-diaminopentane, 1,3-propanediol, butanol, isobutanol and succinic acid) and drugs (artemisinin).Keywords
This publication has 72 references indexed in Scilit:
- Genome‐scale engineering for systems and synthetic biologyMolecular Systems Biology, 2013
- Inhibitory cross-talk upon introduction of a new metabolic pathway into an existing metabolic networkProceedings of the National Academy of Sciences of the United States of America, 2012
- A Whole-Cell Computational Model Predicts Phenotype from GenotypeCell, 2012
- Genome-scale promoter engineering by coselection MAGENature Methods, 2012
- Constraining the metabolic genotype–phenotype relationship using a phylogeny of in silico methodsNature Reviews Microbiology, 2012
- Expanding metabolism for total biosynthesis of the nonnatural amino acid L-homoalanineProceedings of the National Academy of Sciences of the United States of America, 2010
- Elementary mode analysis: a useful metabolic pathway analysis tool for characterizing cellular metabolismApplied Microbiology and Biotechnology, 2009
- Metabolic engineering of Escherichia coli for the production of l -valine based on transcriptome analysis and in silico gene knockout simulationProceedings of the National Academy of Sciences of the United States of America, 2007
- Systems metabolic engineering of Escherichia coli for L ‐threonine productionMolecular Systems Biology, 2007
- Optknock: A bilevel programming framework for identifying gene knockout strategies for microbial strain optimizationBiotechnology & Bioengineering, 2003