Coping with complexity in metabolic engineering

Mampel, Joerg; Buescher, Joerg M.; Meurer, Guido; Eck, Jürgen

doi:10.1016/j.tibtech.2012.10.010

Cited by 32 publications

(32 citation statements)

References 76 publications

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“…Such a lose-to-win scenario exemplifies how intricate metabolic problems can be solved through an unsophisticated regulatory solution that alternates the appearance of divergent pathways rather than merging the two routes or inactivating trouble-making enzymes. Also, such a simple genetic tinkering suggests strategies for orthogonalization of new pathways implanted in a preexisting metabolic chassis by engineering the regulation in a fashion that prevents misrouting or unproductive catalysis (Mampel et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

The differential response of the Pben promoter of Pseudomonas putida mt‐2 to BenR and XylS prevents metabolic conflicts in m‐xylene biodegradation

Pérez‐Pantoja

Kim

Silva‐Rocha

2014

Environmental Microbiology

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Pseudomonas putida mt-2 encompasses two alternative and potentially conflicting routes for benzoate metabolism, one meta pathway encoded by xyl genes of the pWW0 plasmid and mastered by the Pm promoter and XylS, and one chromosomally encoded ortho pathway initiated by Pben and the BenR protein. Any cross-activation of Pben promoter by XylS ought to cause a metabolic conflict during the degradation of m-xylene because 3-methylbenzoate (3MBz) generated as an intermediate can be channelled through the ortho pathway and produce toxic dead-end metabolites. The activation of Pben by XylS was revisited using both reporter technology and tiling arrays targeted to the sequences of interest around messenger RNA initiation of both Pben and Pm promoters. Analysis of supersensitive luxCDABE fusions, inspection of xylX versus benA transcripts and growth tests of benR mutants indicated that the natural expression ranges of XylS under various conditions are insufficient to cause a significant cross-regulation of Pben whether cells face endogenous or exogenous 3MBz. This seems to stem from the nature of the operators for binding either transcriptional factor, which in the case of the Pben promoter of P. putida mt-2 appear to have evolved for avoiding a strong interaction with XylS.

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Section: Discussionmentioning

confidence: 99%

The differential response of the Pben promoter of Pseudomonas putida mt‐2 to BenR and XylS prevents metabolic conflicts in m‐xylene biodegradation

Pérez‐Pantoja

Kim

Silva‐Rocha

2014

Environmental Microbiology

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“…91 Thus, the orthogonal design of pathways would be a direction of coproduction design. 91 Thus, the orthogonal design of pathways would be a direction of coproduction design.…”

Section: Single-cell Biorefinerymentioning

confidence: 99%

Single-Cell Biorefinery

Liang

2015

Industrial Biorefineries &Amp; White Biotechnology

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“…One of the major discoveries was that biological networks follow a hierarchical organization (173) in a modular manner, a feature that, from a holistic perspective, can facilitate interventions and predictions in the network. Recently, the hierarchical organization of biological networks was highlighted as being vital for the reduction of the complexity of bacterial cells for biotechnological applications but under another nomenclature (177). Those authors emphasize the need to introduce the concept of orthogonalization, a classical notion in engineering and mathematics that represents the ability of subsystems of a higher system to function independently, in biology (177).…”

Section: Interactomes and Network Biologymentioning

confidence: 99%

Systems Biology Perspectives on Minimal and Simpler Cells

Xavier

Patil

Rocha

2014

Microbiol Mol Biol Rev

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SUMMARY The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells.

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Coping with complexity in metabolic engineering

Cited by 32 publications

References 76 publications

The differential response of the Pben promoter of Pseudomonas putida mt‐2 to BenR and XylS prevents metabolic conflicts in m‐xylene biodegradation

The differential response of the Pben promoter of Pseudomonas putida mt‐2 to BenR and XylS prevents metabolic conflicts in m‐xylene biodegradation

Single-Cell Biorefinery

Systems Biology Perspectives on Minimal and Simpler Cells

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