Modular optimization of multi-gene pathways for fatty acids production in E. coli.

Abstract:

:Microbial fatty acid-derived fuels have emerged as promising alternatives to petroleum-based transportation fuels. Here we report a modular engineering approach that systematically removed metabolic pathway bottlenecks and led to significant titre improvements in a multi-gene fatty acid metabolic pathway. On the basis of central pathway architecture, E. coli fatty acid biosynthesis was re-cast into three modules: the upstream acetyl coenzyme A formation module; the intermediary acetyl-CoA activation module; and the downstream fatty acid synthase module. Combinatorial optimization of transcriptional levels of these three modules led to the identification of conditions that balance the supply of acetyl-CoA and consumption of malonyl-CoA/ACP. Refining protein translation efficiency by customizing ribosome binding sites for both the upstream acetyl coenzyme A formation and fatty acid synthase modules enabled further production improvement. Fed-batch cultivation of the engineered strain resulted in a final fatty acid production of 8.6 g l(-1). The modular engineering strategies demonstrate a generalized approach to engineering cell factories for valuable metabolites production.

journal_name

Nat Commun

journal_title

Nature communications

authors

Xu P,Gu Q,Wang W,Wong L,Bower AG,Collins CH,Koffas MA

doi

10.1038/ncomms2425

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

1409

issn

2041-1723

pii

ncomms2425

journal_volume

4

pub_type

杂志文章
  • TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma.

    abstract::Antibodies against programmed cell death-1 (PD-1) have considerably changed the treatment for melanoma. However, many patients do not display therapeutic response or eventually relapse. Moreover, patients treated with anti-PD-1 develop immune-related adverse events that can be cured with anti-tumor necrosis factor α (...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02358-7

    authors: Bertrand F,Montfort A,Marcheteau E,Imbert C,Gilhodes J,Filleron T,Rochaix P,Andrieu-Abadie N,Levade T,Meyer N,Colacios C,Ségui B

    更新日期:2017-12-22 00:00:00

  • rec-YnH enables simultaneous many-by-many detection of direct protein-protein and protein-RNA interactions.

    abstract::Knowing which proteins and RNAs directly interact is essential for understanding cellular mechanisms. Unfortunately, discovering such interactions is costly and often unreliable. To overcome these limitations, we developed rec-YnH, a new yeast two and three-hybrid-based screening pipeline capable of detecting interact...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06128-x

    authors: Yang JS,Garriga-Canut M,Link N,Carolis C,Broadbent K,Beltran-Sastre V,Serrano L,Maurer SP

    更新日期:2018-09-14 00:00:00

  • Tuning charge and correlation effects for a single molecule on a graphene device.

    abstract::The ability to understand and control the electronic properties of individual molecules in a device environment is crucial for developing future technologies at the nanometre scale and below. Achieving this, however, requires the creation of three-terminal devices that allow single molecules to be both gated and image...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13553

    authors: Wickenburg S,Lu J,Lischner J,Tsai HZ,Omrani AA,Riss A,Karrasch C,Bradley A,Jung HS,Khajeh R,Wong D,Watanabe K,Taniguchi T,Zettl A,Neto AHC,Louie SG,Crommie MF

    更新日期:2016-11-25 00:00:00

  • Pressure-tuning the quantum spin Hamiltonian of the triangular lattice antiferromagnet Cs2CuCl4.

    abstract::Quantum triangular-lattice antiferromagnets are important prototype systems to investigate numerous phenomena of the geometrical frustration in condensed matter. Apart from highly unusual magnetic properties, they possess a rich phase diagram (ranging from an unfrustrated square lattice to a quantum spin liquid), yet ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09071-7

    authors: Zvyagin SA,Graf D,Sakurai T,Kimura S,Nojiri H,Wosnitza J,Ohta H,Ono T,Tanaka H

    更新日期:2019-03-06 00:00:00

  • Multi-cohort study identifies social determinants of systemic inflammation over the life course.

    abstract::Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relatio...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-08732-x

    authors: Berger E,Castagné R,Chadeau-Hyam M,Bochud M,d'Errico A,Gandini M,Karimi M,Kivimäki M,Krogh V,Marmot M,Panico S,Preisig M,Ricceri F,Sacerdote C,Steptoe A,Stringhini S,Tumino R,Vineis P,Delpierre C,Kelly-Irving M

    更新日期:2019-02-15 00:00:00

  • Variability in the location of high frequency oscillations during prolonged intracranial EEG recordings.

    abstract::The rate of interictal high frequency oscillations (HFOs) is a promising biomarker of the seizure onset zone, though little is known about its consistency over hours to days. Here we test whether the highest HFO-rate channels are consistent across different 10-min segments of EEG during sleep. An automated HFO detecto...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-04549-2

    authors: Gliske SV,Irwin ZT,Chestek C,Hegeman GL,Brinkmann B,Sagher O,Garton HJL,Worrell GA,Stacey WC

    更新日期:2018-06-01 00:00:00

  • Nanofabrication for all-soft and high-density electronic devices based on liquid metal.

    abstract::Innovations in soft material synthesis and fabrication technologies have led to the development of integrated soft electronic devices. Such soft devices offer opportunities to interact with biological cells, mimicking their soft environment. However, existing fabrication technologies cannot create the submicron-scale,...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-14814-y

    authors: Kim MG,Brown DK,Brand O

    更新日期:2020-02-21 00:00:00

  • Asymmetric assembly of high-value α-functionalized organic acids using a biocatalytic chiral-group-resetting process.

    abstract::The preparation of α-functionalized organic acids can be greatly simplified by adopting a protocol involving the catalytic assembly of achiral building blocks. However, the enzymatic assembly of small amino acids and aldehydes to form numerous α-functionalized organic acids is highly desired and remains a significant ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06241-x

    authors: Song W,Wang JH,Wu J,Liu J,Chen XL,Liu LM

    更新日期:2018-09-19 00:00:00

  • Fishing for newly synthesized proteins with phosphonate-handles.

    abstract::Bioorthogonal chemistry introduces affinity-labels into biomolecules with minimal disruption to the original system and is widely applicable in a range of contexts. In proteomics, immobilized metal affinity chromatography (IMAC) enables enrichment of phosphopeptides with extreme sensitivity and selectivity. Here, we a...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17010-0

    authors: Kleinpenning F,Steigenberger B,Wu W,Heck AJR

    更新日期:2020-06-26 00:00:00

  • Oxide-ion conduction in the Dion-Jacobson phase CsBi2Ti2NbO10-δ.

    abstract::Oxide-ion conductors have found applications in various electrochemical devices, such as solid-oxide fuel cells, gas sensors, and separation membranes. Dion-Jacobson phases are known for their rich magnetic and electrical properties; however, there have been no reports on oxide-ion conduction in this family of materia...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15043-z

    authors: Zhang W,Fujii K,Niwa E,Hagihala M,Kamiyama T,Yashima M

    更新日期:2020-03-06 00:00:00

  • A mouse model for a partially inactive obesity-associated human MC3R variant.

    abstract::We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10522

    authors: Lee B,Koo J,Yun Jun J,Gavrilova O,Lee Y,Seo AY,Taylor-Douglas DC,Adler-Wailes DC,Chen F,Gardner R,Koutzoumis D,Sherafat Kazemzadeh R,Roberson RB,Yanovski JA

    更新日期:2016-01-28 00:00:00

  • Distinct pathways mediate axon degeneration during apoptosis and axon-specific pruning.

    abstract::Neurons can activate pathways that destroy the whole cell via apoptosis or selectively degenerate only the axon (pruning). Both apoptosis and axon degeneration require Bax and caspases. Here we demonstrate that despite this overlap, the pathways mediating axon degeneration during apoptosis versus axon pruning are dist...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2910

    authors: Cusack CL,Swahari V,Hampton Henley W,Michael Ramsey J,Deshmukh M

    更新日期:2013-01-01 00:00:00

  • Massive yet grossly underestimated global costs of invasive insects.

    abstract::Insects have presented human society with some of its greatest development challenges by spreading diseases, consuming crops and damaging infrastructure. Despite the massive human and financial toll of invasive insects, cost estimates of their impacts remain sporadic, spatially incomplete and of questionable quality. ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12986

    authors: Bradshaw CJ,Leroy B,Bellard C,Roiz D,Albert C,Fournier A,Barbet-Massin M,Salles JM,Simard F,Courchamp F

    更新日期:2016-10-04 00:00:00

  • Fluctuations between multiple EF-G-induced chimeric tRNA states during translocation on the ribosome.

    abstract::The coupled translocation of transfer RNA and messenger RNA through the ribosome entails large-scale structural rearrangements, including step-wise movements of the tRNAs. Recent structural work has visualized intermediates of translocation induced by elongation factor G (EF-G) with tRNAs trapped in chimeric states wi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8442

    authors: Adio S,Senyushkina T,Peske F,Fischer N,Wintermeyer W,Rodnina MV

    更新日期:2015-06-15 00:00:00

  • Broadband achromatic optical metasurface devices.

    abstract::Among various flat optical devices, metasurfaces have presented their great ability in efficient manipulation of light fields and have been proposed for variety of devices with specific functionalities. However, due to the high phase dispersion of their building blocks, metasurfaces significantly suffer from large chr...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00166-7

    authors: Wang S,Wu PC,Su VC,Lai YC,Hung Chu C,Chen JW,Lu SH,Chen J,Xu B,Kuan CH,Li T,Zhu S,Tsai DP

    更新日期:2017-08-04 00:00:00

  • The Arabidopsis NOT4A E3 ligase promotes PGR3 expression and regulates chloroplast translation.

    abstract::Chloroplast function requires the coordinated action of nuclear- and chloroplast-derived proteins, including several hundred nuclear-encoded pentatricopeptide repeat (PPR) proteins that regulate plastid mRNA metabolism. Despite their large number and importance, regulatory mechanisms controlling PPR expression are poo...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20506-4

    authors: Bailey M,Ivanauskaite A,Grimmer J,Akintewe O,Payne AC,Osborne R,Labandera AM,Etherington RD,Rantala M,Baginsky S,Mulo P,Gibbs DJ

    更新日期:2021-01-11 00:00:00

  • Direct observation of coordinated DNA movements on the nucleosome during chromatin remodelling.

    abstract::ATP-dependent chromatin remodelling enzymes (remodellers) regulate DNA accessibility in eukaryotic genomes. Many remodellers reposition (slide) nucleosomes, however, how DNA is propagated around the histone octamer during this process is unclear. Here we examine the real-time coordination of remodeller-induced DNA mov...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09657-1

    authors: Sabantsev A,Levendosky RF,Zhuang X,Bowman GD,Deindl S

    更新日期:2019-04-12 00:00:00

  • Cephalopod-inspired optical engineering of human cells.

    abstract::Although many animals have evolved intrinsic transparency for the purpose of concealment, the development of dynamic, that is, controllable and reversible, transparency for living human cells and tissues has remained elusive to date. Here, by drawing inspiration from the structures and functionalities of adaptive ceph...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-16151-6

    authors: Chatterjee A,Cerna Sanchez JA,Yamauchi T,Taupin V,Couvrette J,Gorodetsky AA

    更新日期:2020-06-02 00:00:00

  • Time-resolved diffraction of shock-released SiO2 and diaplectic glass formation.

    abstract::Understanding how rock-forming minerals transform under shock loading is critical for modeling collisions between planetary bodies, interpreting the significance of shock features in minerals and for using them as diagnostic indicators of impact conditions, such as shock pressure. To date, our understanding of the for...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01791-y

    authors: Gleason AE,Bolme CA,Lee HJ,Nagler B,Galtier E,Kraus RG,Sandberg R,Yang W,Langenhorst F,Mao WL

    更新日期:2017-11-14 00:00:00

  • Yu-Shiba-Rusinov screening of spins in double quantum dots.

    abstract::A magnetic impurity coupled to a superconductor gives rise to a Yu-Shiba-Rusinov (YSR) state inside the superconducting energy gap. With increasing exchange coupling the excitation energy of this state eventually crosses zero and the system switches to a YSR ground state with bound quasiparticles screening the impurit...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-04683-x

    authors: Grove-Rasmussen K,Steffensen G,Jellinggaard A,Madsen MH,Žitko R,Paaske J,Nygård J

    更新日期:2018-06-18 00:00:00

  • LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling.

    abstract::While the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xe...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09784-9

    authors: Luo J,Wang K,Yeh S,Sun Y,Liang L,Xiao Y,Xu W,Niu Y,Cheng L,Maity SN,Jiang R,Chang C

    更新日期:2019-06-12 00:00:00

  • Dual loss of human POLQ and LIG4 abolishes random integration.

    abstract::Homologous recombination-mediated gene targeting has greatly contributed to genetic analysis in a wide range of species, but is highly inefficient in human cells because of overwhelmingly frequent random integration events, whose molecular mechanism remains elusive. Here we show that DNA polymerase θ, despite its mino...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms16112

    authors: Saito S,Maeda R,Adachi N

    更新日期:2017-07-11 00:00:00

  • Valley interference and spin exchange at the atomic scale in silicon.

    abstract::Tunneling is a fundamental quantum process with no classical equivalent, which can compete with Coulomb interactions to give rise to complex phenomena. Phosphorus dopants in silicon can be placed with atomic precision to address the different regimes arising from this competition. However, they exploit wavefunctions r...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19835-1

    authors: Voisin B,Bocquel J,Tankasala A,Usman M,Salfi J,Rahman R,Simmons MY,Hollenberg LCL,Rogge S

    更新日期:2020-11-30 00:00:00

  • GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance.

    abstract::Efficient engulfment of apoptotic cells is critical for maintaining tissue homoeostasis. When phagocytes recognize 'eat me' signals presented on the surface of apoptotic cells, this subsequently induces cytoskeletal rearrangement of phagocytes for the engulfment through Rac1 activation. However, the intracellular sign...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2540

    authors: Nakaya M,Tajima M,Kosako H,Nakaya T,Hashimoto A,Watari K,Nishihara H,Ohba M,Komiya S,Tani N,Nishida M,Taniguchi H,Sato Y,Matsumoto M,Tsuda M,Kuroda M,Inoue K,Kurose H

    更新日期:2013-01-01 00:00:00

  • RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype.

    abstract::Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. G...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12529-3

    authors: Cai D,Wang J,Gao B,Li J,Wu F,Zou JX,Xu J,Jiang Y,Zou H,Huang Z,Borowsky AD,Bold RJ,Lara PN,Li JJ,Chen X,Lam KS,To KF,Kung HJ,Fiehn O,Zhao R,Evans RM,Chen HW

    更新日期:2019-10-11 00:00:00

  • Autonomous discovery of optically active chiral inorganic perovskite nanocrystals through an intelligent cloud lab.

    abstract::We constructed an intelligent cloud lab that integrates lab automation with cloud servers and artificial intelligence (AI) to detect chirality in perovskites. Driven by the materials acceleration operating system in cloud (MAOSIC) platform, on-demand experimental design by remote users was enabled in this cloud lab. B...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15728-5

    authors: Li J,Li J,Liu R,Tu Y,Li Y,Cheng J,He T,Zhu X

    更新日期:2020-04-27 00:00:00

  • Quantitative operando visualization of the energy band depth profile in solar cells.

    abstract::The energy band alignment in solar cell devices is critically important because it largely governs elementary photovoltaic processes, such as the generation, separation, transport, recombination and collection of charge carriers. Despite the expenditure of considerable effort, the measurement of energy band depth prof...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8745

    authors: Chen Q,Mao L,Li Y,Kong T,Wu N,Ma C,Bai S,Jin Y,Wu D,Lu W,Wang B,Chen L

    更新日期:2015-07-13 00:00:00

  • S-nitrosylation-mediated activation of a histidine kinase represses the type 3 secretion system and promotes virulence of an enteric pathogen.

    abstract::Vibrio parahaemolyticus is the leading cause of seafood-borne diarrheal diseases. Experimental overproduction of a type 3 secretion system (T3SS1) in this pathogen leads to decreased intestinal colonization, which suggests that T3SS1 repression is required for maximal virulence. However, the mechanisms by which T3SS1 ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19506-1

    authors: Gu D,Zhang Y,Wang Q,Zhou X

    更新日期:2020-11-13 00:00:00

  • Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia.

    abstract::Under hypoxia, most of glucose is converted to secretory lactate, which leads to the overuse of glutamine-carbon. However, under such a condition how glutamine nitrogen is disposed to avoid over-accumulating ammonia remains to be determined. Here we identify a metabolic flux of glutamine to secretory dihydroorotate, w...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-08033-9

    authors: Wang Y,Bai C,Ruan Y,Liu M,Chu Q,Qiu L,Yang C,Li B

    更新日期:2019-01-14 00:00:00

  • Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells.

    abstract::Normal epithelial cells are stably connected to each other via the apical junctional complex (AJC). AJCs, however, tend to be disrupted during tumor progression, and this process is implicated in cancer dissemination. Here, using colon carcinoma cells that fail to form AJCs, we investigated molecular defects behind th...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01945-y

    authors: Ito S,Okuda S,Abe M,Fujimoto M,Onuki T,Nishimura T,Takeichi M

    更新日期:2017-11-28 00:00:00