Metabolic engineering articles within Nature Communications

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  • Article
    | Open Access

    An E. coli strain able to use CO2 fixation for sugar synthesis was previously generated by experimental evolution of an engineered strain. Here, Herz et al. show that specific mutations in five genes, encoding carbon metabolism enzymes or key regulators, are sufficient to enable robust growth of the strain.

    • Elad Herz
    • , Niv Antonovsky
    •  & Ron Milo

  • Article
    | Open Access

    Reengineering polyketide synthase encoding genes to produce analogues of natural products can be slow and low-yielding. Here the authors use accelerated evolution to recombine the gene cluster for rapid production of rapamycin-related products.

    • Aleksandra Wlodek
    • , Steve G. Kendrew
    •  & Matthew A. Gregory

  • Article
    | Open Access

    Maleate is an important stock chemical for the production of polymer compounds and pharmaceuticals. Here the authors design a synthetic pathway for maleate in E. coli by combining polyketide biosynthesis and benzene ring cleavage pathways.

    • Shuhei Noda
    • , Tomokazu Shirai
    •  & Akihiko Kondo

  • Article
    | Open Access

    The contribution of metabolic pathways to protein secretion is largely unknown. Here, the authors find conserved metabolic patterns in yeast by examining genome-wide transcriptional responses in high protein secretion mutants and reveal critical factors that can be tuned for efficient protein secretion.

    • Mingtao Huang
    • , Jichen Bao
    •  & Jens Nielsen

  • Article
    | Open Access

    Naturally evolved regulatory circuits have hierarchical layers of signal generation and processing. Here, the authors emulate these networks using feedback-controlled DNA circuits that convert upstream signaling to downstream enzyme activity in a switchable memories circuit.

    • Lenny H. H. Meijer
    • , Alex Joesaar
    •  & Tom F. A. de Greef

  • Article
    | Open Access

    Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

    • Sunil V. Sharma
    • , Xiaoxue Tong
    •  & Rebecca J. M. Goss

  • Article
    | Open Access

    Coupling of growth and product synthesis is an important principle in metabolic engineering, but its range of applicability is unclear. Here, the authors use a dedicated computational framework to study the feasibility of coupling the production of metabolites to growth in the genome-scale metabolic models of five production organisms, and show that coupling can be achieved for most metabolites.

    • Axel von Kamp
    •  & Steffen Klamt

  • Article
    | Open Access

    2,4-Dihydroxybutyric acid has potential to be a precursor to a range of industrially important products, however a natural metabolic pathway for its synthesis does not exist. Here the authors rationally design a synthetic pathway inE. coliby engineering enzymes from malate metabolism.

    • Thomas Walther
    • , Christopher M. Topham
    •  & Jean Marie François

  • Article
    | Open Access

    Terephthalic acid (TPA) is an important commodity chemical typically produced from the oxidation of fossil fuel-derivedp-xylene (pX) at high temperature and pressure. Here the authors report an engineered Escherichia coli strain that can transform pX into TPA with a high conversion yield.

    • Zi Wei Luo
    •  & Sang Yup Lee

  • Article
    | Open Access

    Growth-coupled designs for chemical production are limited by native metabolic networks’ optimality for growth. Here, the authors introduce pathway orthogonality as a measure of the independence of biomass and chemical production pathways, identify metabolic valves that allow substrate utilization to be switched between the two, and demonstrate advantages of orthogonal designs.

    • Aditya Vikram Pandit
    • , Shyam Srinivasan
    •  & Radhakrishnan Mahadevan

  • Article
    | Open Access

    Terpenes are bioactive natural products derived from plants with several commercial applications. Here, the authors engineer a cell-free system composed of 27 enzymes that convert glucose into terpenes, highlighting the potential of synthetic biochemistry approaches for biocompounds production.

    • Tyler P. Korman
    • , Paul H. Opgenorth
    •  & James U. Bowie

  • Article
    | Open Access

    Corynebacterium glutamicum is an important industrial microbe, however it has proven difficult to genetically engineer using Cas9 from Streptococcus pyogenes. Here the authors report effective genome engineering of the bacterium using Cpf1 from Francisella novicida.

    • Yu Jiang
    • , Fenghui Qian
    •  & Sheng Yang

  • Article
    | Open Access

    Genome-scale engineering is a powerful technique for understanding biology and designing microorganisms but has been limited to bacterial species. Here the authors present an automated platform for genome-scale engineering inSaccharomyces cerevisiaeusing CRISPR-Cas and RNAi.

    • Tong Si
    • , Ran Chao
    •  & Huimin Zhao

  • Article
    | Open Access

    Filamentous fungi are a valuable source of natural therapeutic products such as antibiotics. Here the authors engineer monocellularS. cerevisiaeto perform complex secondary metabolism typical of multicellular fungi in order to demonstrate biosynthesis and secretion of bioactive penicillin.

    • Ali R. Awan
    • , Benjamin A. Blount
    •  & Tom Ellis

  • Article
    | Open Access

    The production of short chain fatty acids by microorganisms has numerous industrial and biofuel applications. Here the authors reprogrammeS. cerevisiaefatty acid synthase with five mutations to produce C6- and C8-fatty acids and identify thioesterases responsible for hydrolysis of short chain acyl-CoA hydrolysis.

    • Jan Gajewski
    • , Renata Pavlovic
    •  & Martin Grininger

  • Article
    | Open Access

    Organisms improve their fitness by adjusting their gene expression to the environment, for example bacteria scale the expression of metabolic enzymes near linearly to their growth rate. Here, the authors show that such linear scaling often maximizes growth rate, but that linear scaling is suboptimal under some conditions.

    • Benjamin D. Towbin
    • , Yael Korem
    •  & Uri Alon

  • Article
    | Open Access

    Kinetic models of microbial metabolism have great potential to aid metabolic engineering efforts, but the challenge of parameterization has so far limited them to core metabolism. Here, the authors introduce a genome-scale metabolic model of E. colimetabolism that satisfies fluxomic data for a wild-type and 25 mutant strains in various growth conditions.

    • Ali Khodayari
    •  & Costas D. Maranas

  • Article
    | Open Access

    Directed evolution is a powerful technique for generating improved biological systems through repeated rounds of mutagenesis and selection. Here the authors engineer the yeast retrotransposon Ty1 to enable the creation of large mutant libraries in vivoand use this system to generate improved variants of single enzymes and multigene pathways.

    • Nathan Crook
    • , Joseph Abatemarco
    •  & Hal S. Alper

  • Article
    | Open Access

    Microbial fermentation yield is limited by CO2 loss in glycolysis. Here, the authors engineered Clostridium ljungdahlii for the anaerobic, non-photosynthetic mixotrophy production of acetone, increasing carbon product yield while reducing CO2emissions from a biogenic feedstock fermentation.

    • Shawn W. Jones
    • , Alan G. Fast
    •  & Bryan P. Tracy

  • Article
    | Open Access

    Building multi-component enzymatic processes in one pot is challenged by the inherent complexity of each biochemical system. Here, the authors use online mass spectroscopy and engineering systems theory to achieve forward design of a ten-membered reaction cascade.

    • Christoph Hold
    • , Sonja Billerbeck
    •  & Sven Panke

  • Article
    | Open Access

    Microbial production of isoprene from renewable feedstock is a promising alternative to petroleum-based processes. Here, the authors show that isoprene production in the yeast Saccharomyces cerevisiaecan be improved by dual metabolic engineering of cytoplasmic and mitochondrial acetyl-CoA utilization.

    • Xiaomei Lv
    • , Fan Wang
    •  & Hongwei Yu

  • Article
    | Open Access

    Hereditary tyrosinaemia type I is caused by a gene defect that leads to a lethal accumulation of toxic metabolites in the liver. Here the authors use CRISPR/Cas9 to 'cure' the disease in mice by inactivating another gene, rather than targeting the disease-causing gene itself, to reroute hepatic tyrosine catabolism.

    • Francis P. Pankowicz
    • , Mercedes Barzi
    •  & Karl-Dimiter Bissig

  • Article
    | Open Access

    While yeast is an attractive alternative to bacteria for the production of biofuels it currently has low production yields. Here, the authors systematically engineer Saccharomyces cerevisiae for high-level production of fatty acids, alkanes and fatty alcohols, which are important fuel precursors.

    • Yongjin J. Zhou
    • , Nicolaas A. Buijs
    •  & Jens Nielsen

  • Article
    | Open Access

    Compartmentalization of enzymes into cellular organelles is a promising strategy for improving pathway efficiency. Here, the authors use a high-throughput assay to identify enhanced peroxisomal targeting signals in yeast, and study the effects of peroxisomal compartmentalization on the performance of a model pathway.

    • William C. DeLoache
    • , Zachary N. Russ
    •  & John E. Dueber

  • Article
    | Open Access

    n-Butanol is a valuable biofuel that can be produced industrially by bacterial fermentation. Here the authors uncover a redox-switch within Clostridium acetobutylicum’s thiolase—a key enzyme involved in n-butanol biosynthesis—that controls the rate of fermentative butanol production.

    • Sangwoo Kim
    • , Yu-Sin Jang
    •  & Kyung-Jin Kim

  • Article
    | Open Access

    The effects of protein phosphorylation, a common post-translational modification, are difficult to study using recombinant proteins. Here the authors use genomically engineered E. colito enhance translation systems that express phosphor-serine containing proteins, and use these systems to produce phosphorylated MEK1 kinase.

    • Natasha L. Pirman
    • , Karl W. Barber
    •  & Jesse Rinehart

  • Article
    | Open Access

    Achieving high carbon yields is crucial for biotechnological production of metabolites in engineered microorganisms. Here, Tashiroet al. generate E. colistrains that produce acetyl-CoA and a derived metabolite (isobutyl acetate) in the absence of pyruvate decarboxylation, leading to increased carbon yields.

    • Yohei Tashiro
    • , Shuchi H. Desai
    •  & Shota Atsumi

  • Article
    | Open Access

    Propane is the main component of liquid petroleum gas and has a wide variety of commercial applications. Here, the authors engineer a synthetic metabolic pathway in E. coli, and demonstrate for the first time the renewable production of propane.

    • Pauli Kallio
    • , András Pásztor
    •  & Patrik R. Jones

  • Article |

    The amino acid, L-arginine, has important applications in the food, pharmaceutical and cosmetics industries. Here the authors systematically engineer a Corynebacterium glutamicum strain for the production of L-arginine, and show that their metabolic engineering approach can be used for the industrial production of valuable chemicals.

    • Seok Hyun Park
    • , Hyun Uk Kim
    •  & Sang Yup Lee

  • Article |

    Diatoms are photosynthetic microalgae with underutilized biotechnological potential. Here, the authors carry out targeted gene modifications of lipid metabolism genes in the diatom, Phaeodactylum tricornutum, resulting in a strain that exhibits a 45-fold increase in triacylglycerol accumulation.

    • Fayza Daboussi
    • , Sophie Leduc
    •  & Philippe Duchateau

  • Article
    | Open Access

    The (seco)iridoids and their monoterpenoid indole alkaloid (MIA) derivatives are plant-derived compounds with pharmaceutical applications. Here, the authors identify the last four missing steps of the (seco)iridoid pathway, which they reconstitute in an alternative plant host to produce the complex MIA, strictosidine.

    • Karel Miettinen
    • , Lemeng Dong
    •  & Danièle Werck-Reichhart

  • Article
    | Open Access

    Ionic liquids (ILs) are important solvents in the microbial production of biofuels, but can inhibit microbial growth. Here, the authors transfer newly discovered IL-resistance genes from rain forest soil bacteria to E. coliand report growth and biofuel production at IL levels that are otherwise toxic to native strains.

    • Thomas L. Ruegg
    • , Eun-Mi Kim
    •  & Michael P. Thelen

  • Article |

    Benzylisoquinoline alkaloids are a group of plant secondary metabolites with important pharmaceutical applications. Here, the authors have reconstituted a 10-gene alkaloid pathway in Saccharomyces cerevisiae, demonstrating the feasibility of producing commercially important alkaloids in microbial systems.

    • Elena Fossati
    • , Andrew Ekins
    •  & Vincent J. J. Martin

  • Article |

    Eukaryotic algae and cyanobacteria can produce hydrogen in the presence of little or no oxygen. Here, the authors show that two microalgal strains are capable of producing hydrogen under aerobic conditions, and provide new insights into the natural evolution of oxygen-tolerant hydrogenase.

    • Jae-Hoon Hwang
    • , Hyun-Chul Kim
    •  & Byong-Hun Jeon

  • Article |

    Cells can adapt rapidly to survive and efficiently exploit constantly changing environments by varying their mutation rate. Here the authors construct an in silicosystem to modulate mutation rate, and demonstrate that this method can be used in the laboratory to create specific phenotypes.

    • Howard H. Chou
    •  & Jay D. Keasling

  • Article |

    4-hydroxycoumarin (4HC), a precursor for anticoagulant drugs such as warfarin, has a major role in the treatment of thromboembolic diseases. Here, the authors present an artificial biosynthetic pathway for 4HC production in E. coliand demonstrate its potential for large-scale microbial production.

    • Yuheng Lin
    • , Xiaolin Shen
    •  & Yajun Yan

  • Article |

    Microbial fatty acid-derived fuels represent promising alternatives to the traditionally used fossil fuels. Koffas and colleagues report that E. colicentral metabolism can be modified to produce large quantities of fatty acids through a modular pathway engineering strategy.

    • Peng Xu
    • , Qin Gu
    •  & Mattheos A.G. Koffas

  • Article
    | Open Access

    The ability of oleaginous fungi to produce lipids for biofuels remains untapped, in part due to a lack of genetic information required to engineer industrial strains. Zhuet al. present the genome of R. toruloides, and identify transcriptomic and proteomic changes associated with lipid production.

    • Zhiwei Zhu
    • , Sufang Zhang
    •  & Zongbao K. Zhao

  • Article
    | Open Access

    Advanced biofuels with comparable properties to petroleum-based fuels could be microbially produced from lignocellulosic biomass. In this study,Escherichia coliis engineered to produce bisabolene, the immediate precursor of bisabolane, a biosynthetic alternative to D2 diesel.

    • Pamela P. Peralta-Yahya
    • , Mario Ouellet
    •  & Taek Soon Lee

  • Article
    | Open Access

    Secondary metabolites are widely used in human health and nutrition, but extraction yields from plants are often low. Nakagawaet al. have engineered the metabolism of Escherichia colito develop a fermentation system that produces plant alkaloids from simple carbon sources.

    • Akira Nakagawa
    • , Hiromichi Minami
    •  & Hidehiko Kumagai

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