Abstract：
:Metabolic engineering technology for industrial microorganisms is under development to create rational, more reliable, and more cost-effective approaches to strain improvement. Strain improvement is a critical component of the drug development process, yet the genetic basis for high production by industrial microorganisms is still a mystery. In this study, a search was begun for genetic modifications critical for high-level antibiotic production. The model system used was erythromycin production studied in the unicellular actinomycete, Aeromicrobium erythreum. A tagged-mutagenesis approach allowed reverse engineering of improved strains, revealing two genes, mutB and cobA, in the primary metabolic branch for methylmalonyl-CoA utilization. Knockouts in these genes created a permanent metabolic switch in the flow of methylmalonyl-CoA, from the primary branch into a secondary metabolic branch, driving erythromycin overproduction. The model provides insights into the regulation and evolution of secondary metabolism.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Reeves AR,Cernota WH,Brikun IA,Wesley RK,Weber JMdoi
10.1016/j.ymben.2004.03.003subject
Has Abstractpub_date
2004-10-01 00:00:00pages
300-12issue
4eissn
1096-7176issn
1096-7184pii
S1096717604000266journal_volume
6pub_type
杂志文章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：:The potential to produce succinate aerobically in Escherichia coli would offer great advantages over anaerobic fermentation in terms of faster biomass generation, carbon throughput, and product formation. Genetic manipulations were performed on two aerobic succinate production systems to increase their succinate yield...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2004.10.003
更新日期：2005-03-01 00:00:00
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：:Two types of non-homologous beta-carotene ketolases (CrtW and CrtO) were previously described. We report improvement of a CrtO-type of beta-carotene ketolase for canthaxanthin production in a methylotrophic bacterium, Methylomonas sp. 16a, which could use the C1 substrate (methane or methanol) as sole carbon and energ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2007.05.004
更新日期：2007-07-01 00:00:00
abstract：:Parthenolide, the main bioactive compound of the medicinal plant feverfew (Tanacetum parthenium), is a promising anti-cancer drug. However, the biosynthetic pathway of parthenolide has not been elucidated yet. Here we report on the isolation and characterization of all the genes from feverfew that are required for the...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.03.005
更新日期：2014-05-01 00:00:00
abstract：:An engineered reversal of the β-oxidation cycle (r-BOX) and the fatty acid biosynthesis (FAB) pathway are promising biological platforms for advanced fuel and chemical production in part due to their iterative nature supporting the synthesis of various chain length products. While diverging in their carbon-carbon elon...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.11.003
更新日期：2018-01-01 00:00:00
abstract：:The biosynthesis of non-ribosomal peptides, many of which have pharmaceutical activities, is an evolutionary privilege of microorganisms. Capitalizing on the universal set of the Streptomyces lavendulae non-ribosomal peptide synthase BpsA and the Streptomyces verticillus 4'-phosphopantetheinyl transferase Svp, we have...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.04.002
更新日期：2012-07-01 00:00:00
abstract：:Styrene is an important petroleum-derived molecule that is polymerized to make versatile plastics, including disposable silverware and foamed packaging materials. Finding more sustainable methods, such as biosynthesis, for producing styrene is essential due to the increasing severity of climate change as well as the l...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.05.009
更新日期：2020-09-01 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：:Retroviral vectors released from mouse-derived packaging cell lines are inactivated in human sera by naturally occurring antibodies due to the recognition of Galalpha1,3Galbeta1,4GlcNAc (alphagal-epitope) decorated surface proteins. In this study, an extensive analysis of the glycosylation potential of NIH3T3-derived ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2005.02.004
更新日期：2005-05-01 00:00:00
abstract：:Global gene regulation throughout the Escherichia coli stress response to overexpression of each of five recombinant proteins was evaluated. Reverse-transcriptase polymerase chain reaction-amplified mRNA from induced and control cells were hybridized with a DNA array of Kohara clones representing 16% (700 genes) of th...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.2000.0148
更新日期：2000-07-01 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：:Discovery of the cold-inducible RNA-binding protein (CIRP) in mouse fibroblasts suggests that growth suppression at hypothermic conditions is due to an active response by the cell rather than due to passive thermal effects. To determine the effect of down-regulated CIRP expression on cell growth and erythropoietin (EP...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.11.003
更新日期：2007-03-01 00:00:00
abstract：:Genome-wide or large-scale methodologies employed in functional genomics such as DNA sequencing, transcription profiling, proteomics, and metabolite profiling have become important tools in many metabolic engineering strategies. These techniques allow the identification of genetic differences and insight into their ce...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2003.11.005
更新日期：2004-07-01 00:00:00
abstract：:One of the challenges in strain improvement by evolutionary engineering is to subsequently determine the molecular basis of the improved properties that were enriched from the natural genetic variation during the selective conditions. This study focuses on Saccharomyces cerevisiae IMS0002 which, after metabolic and ev...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2010.08.003
更新日期：2010-11-01 00:00:00
abstract：:Improved supply of farnesyl diphosphate (FPP) is often considered as a typical strategy for engineering Saccharomyces cerevisiae towards efficient terpenoid production. However, in the engineered strains with enhanced precursor supply, the production of the target metabolite is often impeded by insufficient capacity o...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.04.009
更新日期：2015-07-01 00:00:00
abstract：:Biosynthesis of Nylon 12 monomer using dodecanoic acid (DDA) or its esters as the renewable feedstock typically involves ω-hydroxylation, oxidation and ω-amination. The dependence of hydroxylation and oxidation-catalyzing enzymes on redox cofactors, and the requirement of L-alanine as the co-substrate and pyridoxal 5'...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.09.006
更新日期：2020-11-01 00:00:00
abstract：:Aromatic amino acids are precursors of numerous plant secondary metabolites with diverse biological functions. Many of these secondary metabolites are already being used as active pharmaceutical or nutraceutical ingredients, and there are numerous exploratory studies of other compounds with promising applications. p-C...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.08.003
更新日期：2015-09-01 00:00:00
abstract：:A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information e...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/s1096-7176(03)00023-5
更新日期：2003-04-01 00:00:00
abstract：:Cyclic guanosine monophosphate (cGMP) is a universal second messenger that is synthesized from guanosine triphosphate (GTP) by guanylyl cyclases (GCs) and hydrolyzed into guanosine monophosphate (GMP) by phosphodiesterases (PDEs). Small-molecule drugs that induce high cGMP levels in specialized tissues by boosting GC ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.03.016
更新日期：2015-05-01 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：:Lipogenic organisms provide an ideal platform for biodiesel and oleochemical production. Through our previous rational metabolic engineering efforts, lipogenesis titers in Yarrowia lipolytica were significantly enhanced. However, the resulting strain still suffered from decreased biomass generation rates. Here, we emp...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.02.003
更新日期：2015-05-01 00:00:00
abstract：:Control of gene and protein expression of both endogenous and heterologous genes is a key component of metabolic engineering. While a large amount of work has been published characterizing promoters for this purpose, less effort has been exerted to elucidate the role of terminators in yeast. In this study, we characte...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2013.07.001
更新日期：2013-09-01 00:00:00
abstract：:Current studies on microbial isoprene biosynthesis have mostly focused on regulation of the upstream mevalonic acid (MVA) or methyl-erythritol-4-phosphate (MEP) pathway. However, the downstream bottleneck restricting isoprene biosynthesis capacity caused by the weak expression and low activity of plant isoprene syntha...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.12.011
更新日期：2017-01-01 00:00:00
abstract：:Saccharomyces cerevisiae lacks the ability to ferment the pentose sugar xylose that is the second most abundant sugar in nature. Therefore two different xylose catabolic pathways have been heterologously expressed in S. cerevisiae. Whereas the xylose reductase (XR)-xylitol dehydrogenase (XDH) pathway leads to the prod...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2011.05.005
更新日期：2011-09-01 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：:We observed that removing pantothenate (vitamin B5), a precursor to co-enzyme A, from the growth medium of Saccharomyces cerevisiae engineered to produce β-farnesene reduced the strain׳s farnesene flux by 70%, but increased its viability, growth rate and biomass yield. Conversely, the growth rate and biomass yield of ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.07.006
更新日期：2014-09-01 00:00:00
abstract：:Metabolic pathways in cells must be sufficiently robust to tolerate fluctuations in expression levels and changes in environmental conditions. Perturbations in expression levels may lead to system failure due to the disappearance of a stable steady state. Increasing evidence has suggested that biological networks have...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.06.006
更新日期：2014-09-01 00:00:00
abstract：:The intracellular redox state plays an important role in the cellular physiology that determines the efficiency of chemical and biofuel production by microbial cell factories. However, it is difficult to achieve optimal redox rebalancing of synthetic pathways owing to the sensitive responses of cellular physiology acc...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2013.09.003
更新日期：2013-11-01 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
