Recent advances in improving metabolic robustness of microbial cell factories

Jiang, Tianyue; Li, Chenyi; Teng, Yuxi; Zhang, Ruihua; Yan, Yajun

doi:10.1016/j.copbio.2020.06.006

Cited by 38 publications

(20 citation statements)

References 56 publications

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“…Adaptive laboratory evolution (ALE) and genome shuffling are widely used and highly effective tools in tolerance engineering for creating industrial strains resistant to some industrially relevant stress [31][32][33][34][35]. ALE can be used to rapidly evolve and screen robust mutants, and omics analysis can be subsequently be used to investigate the relationship between the strain genotype and phenotype, thereby guiding inverse metabolic engineering.…”

Section: Open Accessmentioning

confidence: 99%

Adaptive laboratory evolution and shuffling of Escherichia coli to enhance its tolerance and production of astaxanthin

Zhou

Liu

2022

Biotechnol Biofuels

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Background Astaxanthin is one of the strongest antioxidants in nature and has been widely used in aquaculture, food, cosmetic and pharmaceutical industries. Numerous stresses caused in the process of a large scale-culture, such as high acetate concentration, high osmolarity, high level of reactive oxygen species, high glucose concentration and acid environment, etc., limit cell growth to reach the real high cell density, thereby affecting astaxanthin production. Results We developed an adaptive laboratory evolution (ALE) strategy to enhance the production of chemicals by improving strain tolerance against industrial fermentation conditions. This ALE strategy resulted in 18.5% and 53.7% increases in cell growth and astaxanthin production in fed-batch fermentation, respectively. Whole-genome resequencing showed that 65 mutations with amino acid substitution were identified in 61 genes of the shuffled strain Escherichia coli AST-4AS. CRISPR interference (CRISPRi) and activation (CRISPRa) revealed that the shuffled strain with higher astaxanthin production may be associated with the mutations of some stress response protein genes, some fatty acid biosynthetic genes and rppH. Repression of yadC, ygfI and rcsC, activation of rnb, envZ and recC further improved the production of astaxanthin in the shuffled strain E. coli AST-4AS. Simultaneous deletion of yadC and overexpression of rnb increased the production of astaxanthin by 32% in the shuffled strain E. coli AST-4AS. Conclusion This ALE strategy will be powerful in engineering microorganisms for the high-level production of chemicals.

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Section: Open Accessmentioning

confidence: 99%

Adaptive laboratory evolution and shuffling of Escherichia coli to enhance its tolerance and production of astaxanthin

Zhou

Liu

2022

Biotechnol Biofuels

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“…The artificially constructed cell factories need to be continuously optimized through the Design-Build-Test-Learn (DBTL) cycle (Nielsen and Keasling, 2016). The DBTL cycle includes new enzyme discovery, heterologous gene expression, promoter engineering, metabolic flux balance, pathway optimization, oxidation and reduction system balance, genome-scale metabolic models and other metabolic engineering strategies (Jiang et al, 2020;Ko et al, 2020;Tang et al, 2020;Wang M. et al, 2020). Finally, a high-yield GA or other natural product microbial cell factory can be obtained.…”

Section: Metabolic Engineering Of S Cerevisiae For Ga Productionmentioning

confidence: 99%

Metabolic Engineering for Glycyrrhetinic Acid Production in Saccharomyces cerevisiae

Guan

Wang

Guan

et al. 2020

Front. Bioeng. Biotechnol.

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Glycyrrhetinic acid (GA) is one of the main bioactive components of licorice, and it is widely used in traditional Chinese medicine due to its hepatoprotective, immunomodulatory, anti-inflammatory and anti-viral functions. Currently, GA is mainly extracted from the roots of cultivated licorice. However, licorice only contains low amounts of GA, and the amount of licorice that can be planted is limited. GA supplies are therefore limited and cannot meet the demands of growing markets. GA has a complex chemical structure, and its chemical synthesis is difficult, therefore, new strategies to produce large amounts of GA are needed. The development of metabolic engineering and emerging synthetic biology provide the opportunity to produce GA using microbial cell factories. In this review, current advances in the metabolic engineering of Saccharomyces cerevisiae for GA biosynthesis and various metabolic engineering strategies that can improve GA production are summarized. Furthermore, the advances and challenges of yeast GA production are also discussed. In summary, GA biosynthesis using metabolically engineered S. cerevisiae serves as one possible strategy for sustainable GA supply and reasonable use of traditional Chinese medical plants.

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“…Developing industrial microorganisms with enhanced robustness properties has been key to achieving economically sustainable fermentation processes for producing chemicals, materials, and fuels. Thus, several reviews have highlighted this topic [ [14] , [15] , [16] , [17] ], but new approaches are constantly being developed. Therefore, this review focuses on the most recent examples of established and emerging methods to improve stress tolerance and robustness of microorganisms, drawing examples mainly from Escherichia coli and yeast Saccharomyces cerevisiae .…”

Section: Introductionmentioning

confidence: 99%

Strategies to increase tolerance and robustness of industrial microorganisms

Mohedano

Konzock

Chen

2022

Synthetic and Systems Biotechnology

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The development of a cost-competitive bioprocess requires that the cell factory converts the feedstock into the product of interest at high rates and yields. However, microbial cell factories are exposed to a variety of different stresses during the fermentation process. These stresses can be derived from feedstocks, metabolism, or industrial production processes, limiting production capacity and diminishing competitiveness. Improving stress tolerance and robustness allows for more efficient production and ultimately makes a process more economically viable. This review summarises general trends and updates the most recent developments in technologies to improve the stress tolerance of microorganisms. We first look at evolutionary, systems biology and computational methods as examples of non-rational approaches. Then we review the (semi-)rational approaches of membrane and transcription factor engineering for improving tolerance phenotypes. We further discuss challenges and perspectives associated with these different approaches.

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Recent advances in improving metabolic robustness of microbial cell factories

Cited by 38 publications

References 56 publications

Adaptive laboratory evolution and shuffling of Escherichia coli to enhance its tolerance and production of astaxanthin

Adaptive laboratory evolution and shuffling of Escherichia coli to enhance its tolerance and production of astaxanthin

Metabolic Engineering for Glycyrrhetinic Acid Production in Saccharomyces cerevisiae

Strategies to increase tolerance and robustness of industrial microorganisms

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