Biotechnology Journal

Cover image for Biotechnology Journal

Special Issue: Systems Metabolic Engineering

May 2013

Volume 8, Issue 5

Pages 505–632, A1–A8

  1. Cover Picture

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    3. Editorial Board
    4. Editorial
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    7. BiotecVisions
    8. Forum
    9. Commentary
    10. Reviews
    11. Research Articles
    12. Meetings
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      Systems Metabolic Engineering

      Article first published online: 2 MAY 2013 | DOI: 10.1002/biot.201390022

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      Special Issue: Systems Metabolic Engineering. Metabolic engineering combines a mix of approaches, including in silico modeling, omics studies, synthetic biology and protein engineering to improve microorganism strains for increased yields and reduced production costs of desirable chemicals. Such an achievement is exemplified on this Special Issue's cover, which shows an electron microscopy image of Corynebacterium glutamicum that has been engineered to produce a sustainable bio-nylon monomer from hemicellulose sugar found in the cell walls of plants. Image provided by Buschke et al.

  2. Editorial Board

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    3. Editorial Board
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      Editorial Board: Biotechnology Journal 5/2013 (page 505)

      Article first published online: 2 MAY 2013 | DOI: 10.1002/biot.201390026

  3. Editorial

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      Editorial: How multiplexed tools and approaches speed up the progress of metabolic engineering (pages 506–507)

      Prof. Hal S. Alper and Prof. Christoph Wittmann

      Article first published online: 2 MAY 2013 | DOI: 10.1002/biot.201300167

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      Systems metabolic engineering is becoming a widely-evoked paradigm for industrial strain design and optimization. Specifically, systems wide experimental and computational analyses of cells and their environments enable guide metabolic engineers to quickly parse the genome and creating desirable overproduction phenotypes.

  4. In this issue

    1. Top of page
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    3. Editorial Board
    4. Editorial
    5. In this issue
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    9. Commentary
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      In this issue (page 508)

      Article first published online: 2 MAY 2013 | DOI: 10.1002/biot.201390023

  5. Contents

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    4. Editorial
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      Contents: Biotechnology Journal 5/2013 (pages 509–510)

      Article first published online: 2 MAY 2013 | DOI: 10.1002/biot.201390024

  6. BiotecVisions

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    5. In this issue
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  7. Forum

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      Book review: Systems Metabolic Engineering (pages 511–512)

      Prof. Hal S. Alper

      Article first published online: 7 JAN 2013 | DOI: 10.1002/biot.201200307

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      Systems Metabolic Enginering, edited by Christoph Wittmann and Sang Yup Lee “sits at the crossroads of being an introductory book providing an overview of the field and a handy desk-reference for state-of-the-art case studies for the expert metabolic engineer”. Read this book review by Hal Alper.

  8. Commentary

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  9. Reviews

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      Recombineering to homogeneity: extension of multiplex recombineering to large-scale genome editing (pages 515–522)

      Nanette R. Boyle, T. Steele Reynolds, Ron Evans, Michael Lynch and Prof. Ryan T. Gill

      Article first published online: 22 FEB 2013 | DOI: 10.1002/biot.201200237

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      Recombineering has enabled fast and efficient editing and rewriting of the chromosome in E. coli; however, the presence of multiple chromosomes requires longer out growth to obtain clonal colonies. The longer outgrowth period can be minimized by changes to the replisome or by performing multiple recombineering events with the same pool of oligos.

    2. Protein design in systems metabolic engineering for industrial strain development (pages 523–533)

      Zhen Chen and Prof. An-Ping Zeng

      Article first published online: 16 APR 2013 | DOI: 10.1002/biot.201200238

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      Within the context of systems metabolic engineering, protein design can be utilized to introduce new enzyme function or substrate spectrum for the construction of novel synthetic pathways. This review discusses tools such as improving enzyme properties for the optimization of pathway efficiency, altering the specificity of transcription regulators or allosteric proteins to rewire regulation network, or building protein scaffolds for metabolite channeling or altering signaling transduction pathways – all of which could be combined to accelerate the process of industrial strain development.

    3. Toward systems metabolic engineering of Aspergillus and Pichia species for the production of chemicals and biofuels (pages 534–544)

      Luis Caspeta and Prof. Jens Nielsen

      Article first published online: 11 APR 2013 | DOI: 10.1002/biot.201200345

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      Metabolic engineering is moving from traditional methods such as random mutagenesis to a systems level which decreases the time and efforts on design and implementation. Here, the authors review the recent trends in systems biology of Aspergillus and Pichia species, highlighting the relevance of developments for systems metabolic engineering of these organisms for the production of hydrolytic enzymes, biofuels and chemicals from biomass.

    4. Protein engineering for metabolic engineering: Current and next-generation tools (pages 545–555)

      Ryan J. Marcheschi, Luisa S. Gronenberg and Prof. James C. Liao

      Article first published online: 16 APR 2013 | DOI: 10.1002/biot.201200371

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      Engineering of proteins for control of metabolism is important to the field of industrial biotechnology. The authors review current and next-generation tools enabling scientists to modify proteins in a rationally designed manner and present several examples of the use of engineered proteins to produce desired compounds via altering the metabolism of living organisms. The use of these tools has shown the promise of protein engineering, and these tools continued development over the next few years will lead to an increase in the numbers and types of chemicals that can be produced by engineered organisms.

  10. Research Articles

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    1. Systems metabolic engineering of xylose-utilizing Corynebacterium glutamicum for production of 1,5-diaminopentane (pages 557–570)

      Nele Buschke, Judith Becker, Rudolf Schäfer, Patrick Kiefer, Rebekka Biedendieck and Prof. Christoph Wittmann

      Article first published online: 16 APR 2013 | DOI: 10.1002/biot.201200367

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      The sustainable production of chemicals from renewable, non-food raw materials is one of the great challenges in industrial biotechnology. In this article, the authors report reprogramming of Corynebacterium glutamicum for efficient 1,5-diaminopentane production from xylose via systems metabolic engineering. Reaching a yield of 32% and a maximum titer of 103 gL–1, the current work reaches a milestone in industrial strain engineering with C. glutamicum.

    2. Integrated transcriptomic and metabolomic analysis of the central metabolism of Synechocystis sp. PCC 6803 under different trophic conditions (pages 571–580)

      Katsunori Yoshikawa, Takashi Hirasawa, Kenichi Ogawa, Yuki Hidaka, Tsubasa Nakajima, Chikara Furusawa and Prof. Hiroshi Shimizu

      Article first published online: 11 APR 2013 | DOI: 10.1002/biot.201200235

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      It is important to understand the cellular metabolism of cyanobacteria for metabolic engineering. In this study, authors perform transcriptomic and metabolomic analyses of the central metabolism of Synechocystis sp. PCC 6803 which was cultured under different trophic conditions. They show that the oxidative pentose phosphate pathway and glycolysis are activated under mixotrophic condition rather than autotrophic condition. By examining the effect of atrazine, they also show that the activity of the glycolytic pathway is decreased due to the indirect effect of atrazine. The omics dataset reported herein provides clues for understanding the metabolism of cyanobacteria.

    3. Deriving metabolic engineering strategies from genome-scale modeling with flux ratio constraints (pages 581–594)

      Jiun Y. Yen, Hadi Nazem-Bokaee, Benjamin G. Freedman, Ahmad I. M. Athamneh and Dr. Ryan S. Senger

      Article first published online: 11 APR 2013 | DOI: 10.1002/biot.201200234

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      Constraining the distribution of a single metabolite among competing pathways can massively reorder global metabolism. In this study, authors show a new method – Flux Balance Analysis with Flux Ratios (FBrAtio) – along with genome-scale modeling, which can be used to determine the global outcome of metabolic engineering strategies. The authors apply this technique to five case studies to evaluate and improve existing metabolic engineering strategies in the production of biofuels and commodity chemicals.

    4. Constraint-based strain design using continuous modifications (CosMos) of flux bounds finds new strategies for metabolic engineering (pages 595–604)

      Cameron Cotten and Prof. Jennifer L. Reed

      Article first published online: 24 APR 2013 | DOI: 10.1002/biot.201200316

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      Strain design algorithms are used to facilitate metabolic engineering efforts by systematically identifying genetic changes, which are needed to make to an organism increase production of a desired chemical. This study presents a new strain design algorithm, which uses continuous modifications (CosMos) and identifies how much fluxes need to change via up/down regulation to guarantee chemical production.

    5. SMET: Systematic multiple enzyme targeting – a method to rationally design optimal strains for target chemical overproduction (pages 605–618)

      David Flowers, R. Adam Thompson, Douglas Birdwell, Dr. Tsewei Wang and Dr. Cong T. Trinh

      Article first published online: 24 APR 2013 | DOI: 10.1002/biot.201200233

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      The Systematic Multiple Enzyme Targeting (SMET) is a novel method to rationally design optimal strains for target chemical overproduction. SMET combines both elementary mode analysis and ensemble metabolic modeling to derive SMET metrics including l- and c-values that can identify rate-limiting reaction steps and suggest which enzymes and how much of these enzymes to manipulate to enhance product yields, titers, and productivities. This method could systematically predict simultaneous multiple enzyme targets and their optimized expression levels, consistent with experimental data from the literature, without performing an iterative sequence of single-enzyme perturbation.

    6. Computational evaluation of Synechococcus sp. PCC 7002 metabolism for chemical production (pages 619–630)

      Trang T. Vu, Eric A. Hill, Leo A. Kucek, Allan E. Konopka, Alexander S. Beliaev and Prof. Jennifer L. Reed

      Article first published online: 24 APR 2013 | DOI: 10.1002/biot.201200315

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      Cyanobacteria are ideal metabolic engineering platforms for carbon-neutral biotechnology. In this study, authors present a thorough computational evaluation of biofuel production in the fast growing cyanobacterium Synechococcus 7002 in terms of yields, energy requirements, and predicted chemical production profiles for knockout mutants under different conditions. Computational strain design methods were able to predict mutants with improved chemical production for most products considered. These predictions will serve as a starting point for future metabolic engineering efforts to construct strains with improved biofuel production.

  11. Meetings

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      Meetings and Conferences: Biotechnology Journal 5/2013 (pages 631–632)

      Article first published online: 2 MAY 2013 | DOI: 10.1002/biot.201390025

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