Abstract:
:The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers and precursors, pharmaceuticals and nutraceuticals, and commodity and specialty chemicals. Much of this rapid expansion in the field has been, in part, due to synergies and advances in the area of systems biology. Specifically, the availability of functional genomics, metabolomics and transcriptomics data has resulted in the potential to produce a wealth of new products, both natural and non-natural, in cellular factories. The sheer amount and diversity of this data however, means that uncovering and unlocking novel chemistries and insights is a non-obvious exercise. To address this issue, a number of computational tools and experimental approaches have been developed to help expedite the design process to create new cellular factories. This review will highlight many of the systems biology enabling technologies that have reduced the design cycle for engineered hosts, highlight major advances in the expanded diversity of products that can be synthesized, and conclude with future prospects in the field of metabolic engineering.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Curran KA,Alper HSdoi
10.1016/j.ymben.2012.04.006subject
Has Abstractpub_date
2012-07-01 00:00:00pages
289-97issue
4eissn
1096-7176issn
1096-7184pii
S1096-7176(12)00049-3journal_volume
14pub_type
杂志文章,评审abstract::Muconic acid (MA) is a dicarboxylic acid used for the production of industrially relevant chemicals such as adipic acid, terephthalic acid, and caprolactam. Because the synthesis of these polymer precursors generates toxic intermediates by utilizing petroleum-derived chemicals and corrosive catalysts, the development ...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2018.02.002
更新日期:2018-03-01 00:00:00
abstract::Acid-tolerant Saccharomyces cerevisiae was engineered to produce lactic acid by expressing heterologous lactate dehydrogenase (LDH) genes, while attenuating several key pathway genes, including glycerol-3-phosphate dehydrogenase1 (GPD1) and cytochrome-c oxidoreductase2 (CYB2). In order to increase the yield of lactic ...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2015.09.006
更新日期:2016-05-01 00:00:00
abstract::A typical characteristic of the butyric acid-producing Clostridium is coproduction of both butyric and acetic acids. Increasing the butyric acid selectivity important for economical butyric acid production has been rather difficult in clostridia due to their complex metabolic pathways. In this work, Clostridium acetob...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2014.03.004
更新日期:2014-05-01 00:00:00
abstract::Isoprene is facing a growing global market due to its wide industrial applications. Current industrial production of isoprene is almost entirely petroleum-based, which is influenced by the shrinking C5 supply, while the natural emission of isoprene is predominantly contributed by plants. To bridge the need gap, a high...
journal_title:Metabolic engineering
pub_type: 杂志文章,评审
doi:10.1016/j.ymben.2016.07.005
更新日期:2016-11-01 00:00:00
abstract::N-linked glycosylation of proteins has both functional and structural significance. Importantly, the glycan structure of a therapeutic protein influences its efficacy, pharmacokinetics, pharmacodynamics and immunogenicity. In this work, we developed glycosylation flux analysis (GFA) for predicting intracellular produc...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2017.07.005
更新日期:2017-09-01 00:00:00
abstract::The promise of plants to serve as the green factories of the future is ever increasing. Plants have been used traditionally for construction, energy, food and feed. Bioactive compounds primarily derived from specialized plant metabolism continue to serve as important scaffold molecules for pharmaceutical drug producti...
journal_title:Metabolic engineering
pub_type: 杂志文章,评审
doi:10.1016/j.ymben.2014.11.005
更新日期:2015-01-01 00:00:00
abstract::The chemical monomer p-hydroxystyrene (pHS) is used for producing a number of important industrial polymers from petroleum-based feedstocks. In an alternative approach, the microbial production of pHS can be envisioned by linking together a number of different metabolic pathways, of which those based on using glucose ...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2007.01.002
更新日期:2007-05-01 00:00:00
abstract::Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a promising biopolyester with good mechanical properties and biodegradability. Large-scale production of PHBV is still hindered by the high production cost. CRISPR/Cas9 method was used to engineer the TCA cycle in Halomonas bluephagenesis on its chromosome for pro...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2019.03.006
更新日期:2019-07-01 00:00:00
abstract::The construction of large DNA molecules that encode pathways, biological machinery, and entire genomes has been limited to the reproduction of natural sequences. However, now that robust methods for assembling hundreds of DNA fragments into constructs > 20 kb are readily available, optimization of large genetic elemen...
journal_title:Metabolic engineering
pub_type: 杂志文章,评审
doi:10.1016/j.ymben.2012.02.005
更新日期:2012-05-01 00:00:00
abstract::One of the important goals of biology is to understand the relationship between DNA sequence information and nonlinear cellular responses. This relationship is central to the ability to effectively engineer cellular phenotypes, pathways, and characteristics. Expression arrays for monitoring total gene expression based...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1006/mben.1999.0115
更新日期:1999-10-01 00:00:00
abstract::Pigmented metabolites have great potential for use in biosensors that target low-resource areas, since sensor output can be interpreted without any equipment. However, full repression of pigment production when undesired is challenging, as even small amounts of enzyme can catalyze the production of large, visible amou...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2017.07.004
更新日期:2017-09-01 00:00:00
abstract::Succinic acid is a platform chemical of recognized industrial value and accordingly faces a continuous challenge to enable manufacturing from most attractive raw materials. It is mainly produced from glucose, using microbial fermentation. Here, we explore and optimize succinate production from sucrose, a globally appl...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2017.10.003
更新日期:2017-11-01 00:00:00
abstract::In this report, UbiE and UbiH in the quinone modification pathway (QMP) were identified in addition to UbiG as bottleneck enzymes in the CoQ10 biosynthesis by Rhodobacter sphaeroides. The CoQ10 content was enhanced after co-overexpression of UbiE and UbiG, however, accompanied by the accumulation of the intermediate 1...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2015.03.012
更新日期:2015-05-01 00:00:00
abstract::Xylose, which is a major constituent of lignocellulosic biomass, was utilized for the production of poly(lactate-co-3-hydroxybutyrate) [P(LA-co-3HB)], having transparent and flexible properties. The recombinant Escherichia coli JW0885 (pflA(-)) expressing LA-polymerizing enzyme (LPE) and monomer supplying enzymes grow...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2012.11.007
更新日期:2013-01-01 00:00:00
abstract::FK506, a widely used immunosuppressant, is produced by industrial fermentation processes using various Streptomyces species. Independently of the strain, structurally related compound FK520 is co-produced, resulting in complex and costly isolation procedures. In this paper, we report a chemobiosynthetic approach for e...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2011.11.003
更新日期:2012-01-01 00:00:00
abstract::Ethyl acetate is an industrially relevant ester that is currently produced exclusively through unsustainable processes. Many yeasts are able to produce ethyl acetate, but the main responsible enzyme has remained elusive, hampering the engineering of novel production strains. Here we describe the discovery of a new enz...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2017.03.004
更新日期:2017-05-01 00:00:00
abstract::Methanol is a promising feedstock for bioproduction of fuels and chemicals, thus massive efforts have been devoted to engineering non-native methylotrophic platform microorganisms to utilize methanol. Herein, we rationally designed and experimentally engineered the industrial workhorse Corynebacterium glutamicum to se...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2018.07.011
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:6-Methylsalicylic acid synthase (MSAS), a fungal polyketide synthase from Penicillium patulum, is perhaps the simplest polyketide synthase that embodies several hallmarks of this family of multifunctional enzymes--a large multidomain protein, a high degree of specificity toward acetyl-CoA and malonyl-CoA sub...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1006/mben.1999.0113
更新日期:1999-04-01 00:00:00
abstract::Isotopically nonstationary metabolic flux analysis (INST-MFA) provides a versatile platform to quantitatively assess in vivo metabolic activities of autotrophic systems. By applying INST-MFA to recombinant aldehyde-producing cyanobacteria, we identified metabolic alterations that correlated with increased strain perfo...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2020.03.007
更新日期:2020-07-01 00:00:00
abstract::13C metabolic flux analysis (13C-MFA) is a widely used tool for quantitative analysis of microbial and mammalian metabolism. Until now, 13C-MFA was based mainly on measurements of isotopic labeling of amino acids derived from hydrolyzed biomass proteins and isotopic labeling of extracted intracellular metabolites. Her...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2016.06.007
更新日期:2016-11-01 00:00:00
abstract::Fucosyllactoses (FLs), present in human breast milk, have been reported to benefit human health immensely. Especially, 3-fucosyllactose (3-FL) has numerous benefits associated with a healthy gut ecosystem. Metabolic engineering of microorganisms is thought to be currently the only option to provide an economically fea...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2018.05.021
更新日期:2018-07-01 00:00:00
abstract::Cyanobacteria hold promise as a cell factory for producing biofuels and bio-derived chemicals, but genome engineering of cyanobacteria such as Synechococcus elongatus PCC 7942 poses challenges because of their oligoploidy nature and long-term instability of the introduced gene. CRISPR-Cas9 is a newly developed RNA-gui...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2016.09.006
更新日期:2016-11-01 00:00:00
abstract::Punicic acid (PuA; 18:3Δ9cis,11trans,13cis), a conjugated linolenic acid isomer bearing three conjugated double bonds, is associated with various health benefits and has potential for industrial use. The major nature source of this unusual fatty acid is pomegranate (Punica granatum) seed oil, which contains up to 80% ...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2020.08.011
更新日期:2020-11-01 00:00:00
abstract::Glucose pulse experiments at seconds time scale resolution were performed in aerobic glucose-limited Escherichia coli chemostat cultures. The dynamic responses of oxygen-uptake and growth rate at seconds time scale were determined using a new method based on the dynamic liquid-phase mass balance for oxygen and the pse...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2011.03.003
更新日期:2011-05-01 00:00:00
abstract::We have isolated a new extremely thermophilic fast-growing Geobacillus strain that can efficiently utilize xylose, glucose, mannose and galactose for cell growth. When grown aerobically at 72 °C, Geobacillus LC300 has a growth rate of 2.15 h(-1) on glucose and 1.52 h(-1) on xylose (doubling time less than 30 min). The...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2015.09.009
更新日期:2015-11-01 00:00:00
abstract::A methionine-producing strain was derived from a lysine-producing Corynebacterium glutamicum through a process of genetic manipulation in order to assess its potential to synthesize and accumulate methionine during growth. The strain carries a deregulated hom gene (hom(FBR)) to abolish feedback inhibition of homoserin...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2007.05.001
更新日期:2007-07-01 00:00:00
abstract::Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2011.09.008
更新日期:2011-11-01 00:00:00
abstract::Engineering cellular metabolism for improved production of valuable chemicals requires extensive modulation of bacterial genome to explore complex genetic spaces. Here, we report the development of a CRISPR-Cas9 based method for iterative genome editing and metabolic engineering of Escherichia coli. This system enable...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2015.06.006
更新日期:2015-09-01 00:00:00
abstract::Microbial fermentation conditions are dynamic, due to transcriptional induction, nutrient consumption, or changes to incubation conditions. In this study, 13C-metabolic flux analysis was used to characterize two violacein-producing E. coli strains with vastly different productivities, and to profile their metabolic ad...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2016.12.008
更新日期:2017-01-01 00:00:00
abstract::Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulat...
journal_title:Metabolic engineering
pub_type: 杂志文章
doi:10.1016/j.ymben.2017.06.002
更新日期:2017-07-01 00:00:00