Identifying gene targets for the metabolic engineering of lycopene biosynthesis in Escherichia coli

Alper, Hal S.; Liu, Jing Jing; Moxley, Joel F.; Stephanopoulos, Gregory

doi:10.1016/j.ymben.2004.12.003

Cited by 416 publications

(263 citation statements)

References 29 publications

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“…The majority of the research in this area has come from studies of pharmaceutically important compounds such as lycopene, carotenoids, sterols, taxol and artemisinin [44,[46][47][48]. High-level production of IPP has been achieved in both E. coli and S. cerevisiae, and many different iso-prenoids have been produced with the use of these engin-eered hosts [49][50][51][52][53].…”

Section: The Isoprenoid Pathwaymentioning

confidence: 99%

Biofuel alternatives to ethanol: pumping the microbial well

Fortman

Chhabra

Mukhopadhyay

et al. 2008

Trends in Biotechnology

338

209

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Section: The Isoprenoid Pathwaymentioning

confidence: 99%

Biofuel alternatives to ethanol: pumping the microbial well

Fortman

Chhabra

Mukhopadhyay

et al. 2008

Trends in Biotechnology

338

209

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“…Applications of the E. coli GEM range from pragmatic to theoretical studies, and can be classified into five general categories ( Fig. 3): 1) metabolic engineering [20][21][22][23][24][25][26][27][28][29][30] ; 2) biological discovery [31][32][33][34][35][36][37] ; 3) assessment of phenotypic behavior 19, ; 4) biological network analysis [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79] ; and 5) studies of bacterial evolution [80][81][82] . The in silico methods used to probe the E. coli GEM in each study are summarized in Fig.…”

Section: Ask Not What You Can Do For a Reconstruction But What A Recmentioning

confidence: 99%

“…Through the application of computational methods that incorporate linear, mixed integer linear, and non-linear programming, it has been demonstrated that model-directed strain design can lead to increased metabolite production [20][21][22][23][24][25][26][27][28][29][30] . In these studies, the E. coli GEM is principally used to analyze the metabolite production potential of E. coli and identify metabolic interventions needed to enable the production of the product of interest.…”

Section: Applications Of Gems To Metabolic Engineering Of E Colimentioning

confidence: 99%

“…In these studies, the E. coli GEM is principally used to analyze the metabolite production potential of E. coli and identify metabolic interventions needed to enable the production of the product of interest. Thus, E. coli strains have been systematically designed through in silico analysis to overproduce target metabolites such as lycopene 23,24 , lactic acid 25 , ethanol 26 , succinic acid 27,28 , Lvaline 29 , L-threonine 30 , additional amino acids 21 , as well as diverse products from hydrogen to vanillin 22 . Select exemplary metabolic engineering applications will be described in more detail.…”

Section: Applications Of Gems To Metabolic Engineering Of E Colimentioning

confidence: 99%

“…Strain performance was evaluated by monitoring lycopene production through enzymatic assays and mutant growth rates. In addition, the strain designs identified computationally were compared to mixed combinatorial transposon mutagenesis and it was found that the maximum production observed could be designed solely using the systematic GEM aided computational method 23,24 . Furthermore, a deleterious effect was observed when targets identified in individual computational designs were combined in an attempt to achieve an overall more desirable phenotype.…”

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The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli

2008

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The number and scope of methods developed to interrogate and use metabolic network reconstructions has significantly expanded since the first review of the use of constraint-based analysis in Nature Biotechnology some 14 years ago. In particular, the Escherichia coli metabolic network reconstruction has reached the genome-scale and has been broadly adapted. Specifically, it has been used to address a broad spectrum of basic and practical applications, falling into five main categories: 1) metabolic engineering, 2) model-directed discovery, 3) interpretations of phenotypic screens, 4) analysis of network properties, and 5) studies of evolutionary processes. With these accomplishments in hand, the field is expected to move forward and seek to further, i) broaden the scope and content of network reconstructions, ii) develop new and novel in silico analysis tools, and iii) expand in adaptation to uses of proximal and distal causation in biology. Taken together, these efforts will solidify a mechanistic genotype-phenotype relationship for microbial metabolism.The availability of reconstructed metabolic networks for microorganisms has increased rapidly in recent years, and a growing number of research groups are reconstructing metabolic networks for organisms of interest 1 . A network reconstruction represents a highly curated set of primary biological information for a particular organism and thus can be considered a biochemically, genetically and genomically structured (BiGG) data base 1, 2 . A curated BiGG data base (de facto a knowledge base) can be converted into a mathematical format (i.e., an in silico model), and used to computationally assess phenotypic properties using a variety of computational methods 2,3 . Genome-scale reconstructions are thus, a key step in quantifying the genotype-phenotype relationship and can be used to 'bring genomes to life' 4 . The purpose of this review is to summarize and classify applications utilizing the E. coli reconstruction to answer a broad spectrum of biological questions. These studies provide both an up to date review of the applications of constraint-based analysis and a guide to similar applications for the growing number of organisms for which genome-scale reconstructions are becoming available. The Key Steps in the Formulation of Genome-scale Metabolic Network ModelsThe four key steps in the formulation and use of genome-scale models are illustrated in Fig. 1. Foundational to the process is the generation of global, or genome-scale, omics data. Omics data, along with legacy information (i.e., the 'bibliome') and small-scale detailed experiments, can be used to define the interactions amongst the biological components that are used to reconstruct organism-specific networks 1 . Network reconstruction is also an iterative, on-going process that continually integrates data in a formal fashion as it becomes available 5 . As a result, a current and well curated genome-scale network reconstruction is a common denominator for those studying systems biology of an or...

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Carotenoids, Microbial Processes

Schmidt‐Dannert

Lee

2009

Encyclopedia of Industrial Biotechnology

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Carotenoids are used commercially as food colorants, feed supplements, nutraceuticals, and for cosmetic and pharmaceutical purposes. However, only a handful of the more than several hundred different carotenoids identified in nature can be obtained in useful quantities by chemical synthesis, extraction from their natural sources or microbial fermentation. The current global market for all commercially used carotenoids is expected to rise at an average annual growth rate of 2.9% reaching over $1 billion in 2009. The over‐the‐counter and pharmaceutical sector has become a new market for carotenoids and, together with an increasing demand for carotenoids in traditional feed and food applications, pushes efforts for the production of diverse carotenoid structures in useful quantities. As an alternative to chemical synthesis and extraction from natural sources, microbial processes are being currently developed for the production of carotenoids. In this article we will discuss the recent progress made in the development of microbial processes for carotenoid production.

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Identifying gene targets for the metabolic engineering of lycopene biosynthesis in Escherichia coli

Cited by 416 publications

References 29 publications

Biofuel alternatives to ethanol: pumping the microbial well

Biofuel alternatives to ethanol: pumping the microbial well

The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli

Carotenoids, Microbial Processes

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