Abstract:
:Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenges have been the time-, cost- and labor-intensive processes of strain development owing to the difficulties in understanding complex interactions among the metabolic, gene regulatory and signaling networks at the cell level, which are collectively represented as overall system performance under industrial fermentation conditions. These challenges can be overcome by taking systems approaches through the use of state-of-the-art tools of systems biology, synthetic biology and evolutionary engineering in the context of industrial bioprocess. Major systems metabolic engineering achievements in recent years include microbial production of amino acids (L-valine, L-threonine, L-lysine and L-arginine), bulk chemicals (1,4-butanediol, 1,4-diaminobutane, 1,5-diaminopentane, 1,3-propanediol, butanol, isobutanol and succinic acid) and drugs (artemisinin).
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Lee SY,Kim HUdoi
10.1038/nbt.3365subject
Has Abstractpub_date
2015-10-01 00:00:00pages
1061-72issue
10eissn
1087-0156issn
1546-1696pii
nbt.3365journal_volume
33pub_type
杂志文章,评审abstract::How intrinsic gene-regulatory networks interact with a cell's spatial environment to define its identity remains poorly understood. We developed an approach to distinguish between intrinsic and extrinsic effects on global gene expression by integrating analysis of sequencing-based and imaging-based single-cell transcr...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4260
更新日期:2018-10-29 00:00:00
abstract::Nucleotide variants, especially those related to epigenetic functions, provide critical regulatory information beyond simple genomic sequence, and they define cell status in higher organisms. 5-Methylcytosine, which is found in DNA, was until recently the only nucleotide variant studied in terms of epigenetics in euka...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.2398
更新日期:2012-11-01 00:00:00
abstract::The discovery of large multiprotein complexes in cells has increased the demand for improved heterologous protein production techniques to study their molecular structure and function. Here we describe MultiBac, a simple and versatile system for generating recombinant baculovirus DNA to express protein complexes compr...
journal_title:Nature biotechnology
pub_type: 信件
doi:10.1038/nbt1036
更新日期:2004-12-01 00:00:00
abstract::Nitrile hydratase (NHase), which catalyzes the hydration of nitriles to amides, has been used in the industrial production of acrylamide and nicotinamide. Recent studies on NHases, which are roughly classified into iron and cobalt types according to the metal involved, have clarified the photoactivation mechanism, the...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt0898-733
更新日期:1998-08-01 00:00:00
abstract::High-density short oligonucleotide microarrays have become a widely used tool for measuring gene expression on a large scale. However, details of the mechanism of binding on microarrays remain unclear. Short oligonucleotide probes currently synthesized on microarrays are often ineffective as a result of limited sequen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt836
更新日期:2003-07-01 00:00:00
abstract::Analysis of abnormally methylated genes is increasingly important in basic research and in the development of cancer biomarkers. We have developed methyl-BEAMing technology to enable absolute quantification of the number of methylated molecules in a sample. Individual DNA fragments are amplified and analyzed either by...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1559
更新日期:2009-09-01 00:00:00
abstract::Transplantation of oligodendrocyte precursor cells (OPCs) is a promising potential therapeutic strategy for diseases affecting myelin. However, the derivation of engraftable OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily available. Here we report the generation of induced ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2564
更新日期:2013-05-01 00:00:00
abstract::A human pancreatic beta-cell line that is functionally equivalent to primary beta-cells has not been available. We established a reversibly immortalized human beta-cell clone (NAKT-15) by transfection of primary human beta-cells with a retroviral vector containing simian virus 40 large T-antigen (SV40T) and human telo...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1145
更新日期:2005-10-01 00:00:00
abstract::As the cost of human genome sequencing plunges and large-scale genome-phenotype studies become possible, society should do more to reward those individuals who choose to disclose their data, despite the risks. ...
journal_title:Nature biotechnology
pub_type: 评论,社论
doi:10.1038/nbt0909-777
更新日期:2009-09-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature biotechnology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41587-020-0427-1
更新日期:2020-03-01 00:00:00
abstract::We introduce Sailfish, a computational method for quantifying the abundance of previously annotated RNA isoforms from RNA-seq data. Because Sailfish entirely avoids mapping reads, a time-consuming step in all current methods, it provides quantification estimates much faster than do existing approaches (typically 20 ti...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2862
更新日期:2014-05-01 00:00:00
abstract::The density and long-term stability of DNA make it an appealing storage medium, particularly for long-term data archiving. Existing DNA storage technologies involve the synthesis and sequencing of multiple nominally identical molecules in parallel, resulting in information redundancy. We report the development of enco...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0240-x
更新日期:2019-10-01 00:00:00
abstract::Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE site...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/6981
更新日期:1999-03-01 00:00:00
abstract::Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3052
更新日期:2014-12-01 00:00:00
abstract::While the use of enzymes as biocatalysts to assist in the industrial manufacture of fine chemicals and pharmaceuticals has enormous potential, application is frequently limited by evolution-led catalyst traits. The advent of designer biocatalysts, produced by informed selection and mutation through recombinant DNA tec...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt0102-37
更新日期:2002-01-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature biotechnology
pub_type: 已发布勘误
doi:10.1038/s41587-019-0320-y
更新日期:2019-12-01 00:00:00
abstract::Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strai...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2858
更新日期:2014-04-01 00:00:00
abstract::Little is known about the potential of plastids to accomplish post-translational modifications of foreign proteins. In the present study we generated transplastomic tobacco plants that accumulate the outer surface lipoprotein A (OspA)-the basic constituent of the first generation monovalent human vaccine against Lyme ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1170
更新日期:2006-01-01 00:00:00
abstract::We have developed a platform for cell analysis based on immunomagnetic selection and magnetic alignment of cells in combination with an epi-illumination tracking and detection system. Whole blood was labeled with ferromagnetic nanoparticles and fluorescent probes, and placed in a magnetic field in a chamber. Cells lab...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/70761
更新日期:1999-12-01 00:00:00
abstract::Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult. Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed compr...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2890
更新日期:2014-05-01 00:00:00
abstract::For the past five decades, the need for new antibiotics has been met largely by semisynthetic tailoring of natural product scaffolds discovered in the middle of the 20(th) century. More recently, however, advances in technology have sparked a resurgence in the discovery of natural product antibiotics from bacterial so...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt1266
更新日期:2006-12-01 00:00:00
abstract::Efficient delivery of small interfering (si)RNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application. We show that siRNA synthetically linked to a CpG oligonucleotide agonist of toll-like receptor (TLR)9 targets and silences genes in TLR9(+) myeloid cells and B ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1564
更新日期:2009-10-01 00:00:00
abstract::We report a protocol for the rapid identification of DNA-binding proteins. Immobilized DNA probes harboring a specific sequence motif are incubated with cell or nuclear extract. Proteins are analyzed directly off the solid support by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The det...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/12873
更新日期:1999-09-01 00:00:00
abstract::The interaction between the HSP90 chaperone and its client kinases is sensitive to the conformational status of the kinase, and stabilization of the kinase fold by small molecules strongly decreases chaperone interaction. Here we exploit this observation and assay small-molecule binding to kinases in living cells, usi...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2620
更新日期:2013-07-01 00:00:00
abstract::The basics of determining valuation will help you to understand what criteria matter most for investors. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:
更新日期:2004-08-01 00:00:00
abstract::Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 gene...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3514
更新日期:2016-05-01 00:00:00
abstract::The functional state of a cell is largely determined by the spatiotemporal organization of its proteome. Technologies exist for measuring particular aspects of protein turnover and localization, but comprehensive analysis of protein dynamics across different scales is possible only by combining several methods. Here w...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2281
更新日期:2012-06-24 00:00:00
abstract::Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0322-9
更新日期:2020-02-01 00:00:00
abstract::Isolating antigen-specific T lymphocytes is hampered by the low frequency of the cells and the low affinity between T-cell receptors (TCR) and antigen. We describe the isolation and purification of antigen-specific CD8+ T lymphocytes from mixed T-cell populations. Magnetic beads coated with major histocompatibility co...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0398-281
更新日期:1998-03-01 00:00:00
abstract::Human embryonic stem cells (hESCs) have two properties of interest for the development of cell therapies: self-renewal and the potential to differentiate into all major lineages of somatic cells in the human body. Widespread clinical application of hESC-derived cells will require culture methods that are low-cost, rob...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1629
更新日期:2010-06-01 00:00:00