Engineering modular ester fermentative pathways in Escherichia coli

Layton, Donovan S.; Trinh, Cong T.

doi:10.1016/j.ymben.2014.09.006

Cited by 92 publications

(132 citation statements)

References 64 publications

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“…Enforcing obligate coupling of growth with product synthesis has become a key principle for the targeted modification of microorganisms [2,3,6,7,10,13,16,21,22,23,25,27,28,29,31,32,38,39,40,41]. The goal is to delete some reactions such that the host organism can only grow if it synthesizes a desired compound as a mandatory by-product.…”

Section: Introductionmentioning

confidence: 99%

On the feasibility of growth-coupled product synthesis in microbial strains

Klamt

Mahadevan

2015

Metabolic Engineering

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Section: Introductionmentioning

confidence: 99%

On the feasibility of growth-coupled product synthesis in microbial strains

Klamt

Mahadevan

2015

Metabolic Engineering

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“…The best of the 122 full-length pathways tested resulted in recovery of 57% of the wild-type activity. Layton and Trinh used Gibson cloning to make ester fermentative pathways in E. coli 33 . Their modular design of their pathway allowed quick replacement of RBS and promoter sequences.…”

Section: Enabling Dna Construction Methodsmentioning

confidence: 99%

High-throughput evaluation of synthetic metabolic pathways

Klesmith

Whitehead

2016

Technology

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A central challenge in the field of metabolic engineering is the efficient identification of a metabolic pathway genotype that maximizes specific productivity over a robust range of process conditions. Here we review current methods for optimizing specific productivity of metabolic pathways in living cells. New tools for library generation, computational analysis of pathway sequence-flux space, and high-throughput screening and selection techniques are discussed.

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“…[1,[8][9][10] This modular cell design approach, known as ModCell, uses multi-objective optimization to account for the competing cellular objectives when cellular metabolism is (re)designed in a modular fashion to produce a diverse class of target chemicals. ModCell has been experimentally demonstrated for biosynthesis of alcohols [8,11,12] and esters [13][14][15][16][17] in Escherichia coli.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Multi-objective Evolutionary Algorithms to Solve the Modular Cell Design Problem for Novel Biocatalysis

Garcia

Trinh

2019

Preprint

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A large space of chemicals with broad industrial and consumer applications could be synthesized by engineered microbial biocatalysts. However, the current strain optimization process is prohibitively laborious and costly to produce one target chemical and often requires new engineering efforts to produce new molecules. To tackle this challenge, modular cell design based on a chassis strain that can be combined with different product synthesis pathway modules has been recently proposed. This approach seeks to minimize unexpected failure and avoid task repetition, leading to a more robust and faster strain engineering process. The modular cell design problem was mathematically formulated using a multi-objective optimization framework.[1] In this study, we evaluated a library of the state-of-the-art multi-objective evolutionary algorithms (MOEAs) to identify the most effective method to solve the modular cell design problem. Using the best MOEA, we found better solutions for modular cells compatible with many product synthesis modules. Furthermore, the best performing algorithm could provide better and more diverse design options that might help increase the likelihood of successful experimental implementation. We identified key parameter configurations to overcome the difficulty associated with multi-objective optimization problems with many competing design objectives. Interestingly, we found that MOEA performance with a real application problem, e.g., the modular strain design problem, does not always correlate with artificial benchmarks. Overall, MOEAs provide powerful tools to solve the modular cell design problem for novel biocatalysis.

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Engineering modular ester fermentative pathways in Escherichia coli

Cited by 92 publications

References 64 publications

On the feasibility of growth-coupled product synthesis in microbial strains

On the feasibility of growth-coupled product synthesis in microbial strains

High-throughput evaluation of synthetic metabolic pathways

Comparison of Multi-objective Evolutionary Algorithms to Solve the Modular Cell Design Problem for Novel Biocatalysis

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