Directed evolution: an evolving and enabling synthetic biology tool

Cobb, Ryan E.; Si, Tong; Zhao, Huimin

doi:10.1016/j.cbpa.2012.05.186

Cited by 93 publications

(54 citation statements)

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“…Details of specific techniques available for systems metabolic engineering have been thoroughly reviewed elsewhere, so are not discussed here (for reviews, see refs. 4,[19][20][21][22][23][24][25][26].…”

mentioning

confidence: 99%

Systems strategies for developing industrial microbial strains

Lee¹,

2015

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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).

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confidence: 99%

Systems strategies for developing industrial microbial strains

Lee¹,

2015

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“…3 In this regard, many directed evolution techniques such as error-prone PCR, site-directed saturation mutagenesis, iterative saturation mutagenesis, and DNA shuffling have been developed and widely used to optimize many catalytic parameters including thermostability, activity, substrate specificity, and enantioselectivity in artificial environments. 4,5 In addition, the construction of robust cell factories for whole-cell biocatalysis or de novo synthesis of the target products with an optimized background is also attractive and indispensable. As a result, many studies to improve the titer of target products or cell resistance to environments by genome engineering with the abovementioned directed evolution techniques have been reported.…”

Section: Traditional Approaches For the Directed Evolution Of Genomesmentioning

confidence: 99%

Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes

Kang¹,

Zhang

Jin

et al. 2015

Bioengineered

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“…The process mimics Darwinian evolution in a test tube and involves iterative rounds of creating genetic diversity followed by selection or screening (Cobb et al, 2012; Rubin-Pitel, 2006; Wang et al, 2012) (Fig. 1A).…”

Section: Tools For Protein Engineeringmentioning

confidence: 99%

“…Next, a few examples will be highlighted to illustrate how these tools can be used to improve the efficiency of pathways for the production of fuels and chemicals. Though there are innumerable examples of protein engineering to improve the performance of enzyme biocatalysts (Bornscheuer et al, 2012; Cobb et al, 2012; Rubin-Pitel and Zhao, 2006; Wang et al, 2012), this review will focus on engineering enzymes within a pathway, wherein the engineered enzyme is coupled with the entire pathway for an increased flux, titer, and productivity of the final product. Protein design for biosensor development and signaling pathway engineering will also be discussed, as systems can be engineered to yield novel output responses or react to novel inputs.…”

Section: Introductionmentioning

confidence: 99%

Protein design for pathway engineering

Eriksen

Lian

Zhao

2014

Journal of Structural Biology

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Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds.

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Directed evolution: an evolving and enabling synthetic biology tool

Cited by 93 publications

References 54 publications

Systems strategies for developing industrial microbial strains

Systems strategies for developing industrial microbial strains

Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes

Protein design for pathway engineering

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