Genetically engineered yeasts as a new delivery vehicle of active compounds to the digestive tract: in vivo validation of the concept in the rat.

Abstract:

:An innovative "biodrug" concept based on oral administration of living recombinant microorganisms as a vehicle to deliver active compounds directly into the digestive tract has recently been developed. To validate this concept, we studied a recombinant Saccharomyces cerevisiae strain in order to investigate its viability and its ability to produce a protein (glutathione-S-transferase (GST)-V(5)H(6)) in the rat. Following oral administration, the recombinant yeast showed a survival rate of around 40% in the upper parts of the digestive tract, but was more sensitive to the conditions in the large intestinal, where viability dropped to 1%. Western blot analysis was able to detect the model protein throughout the digestive tract, including stomach, duodenum, jejunum (proximal, median and distal), ileum, cecum and colon. The gastrointestinal sac technique was employed to quantify GST-V(5)H(6) in all the digestive compartments. These results suggest that S. cerevisiae may represent a useful host for producing compounds of interest directly in the digestive tract.

journal_name

Metab Eng

journal_title

Metabolic engineering

authors

Garrait G,Jarrige JF,Blanquet-Diot S,Alric M

doi

10.1016/j.ymben.2009.01.001

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

148-54

issue

3

eissn

1096-7176

issn

1096-7184

pii

S1096-7176(09)00006-8

journal_volume

11

pub_type

杂志文章
  • Generation of serum-stabilized retroviruses: reduction of alpha1,3gal-epitope synthesis in a murine NIH3T3-derived packaging cell line by expression of chimeric glycosyltransferases.

    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

    authors: Hansen W,Grabenhorst E,Nimtz M,Müller K,Conradt HS,Wirth M

    更新日期:2005-05-01 00:00:00

  • A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

    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

    authors: Wang J,Cui X,Yang L,Zhang Z,Lv L,Wang H,Zhao Z,Guan N,Dong L,Chen R

    更新日期:2017-07-01 00:00:00

  • The organization of metabolic reaction networks. II. Signal processing in hierarchical structured functional units.

    abstract::Based on the analysis of molecular interactions of proteins with DNA binding sites, a new approach to developing mathematical models describing gene expression is introduced. Detection of hierarchical structures in metabolic networks can be used to decompose complex reaction schemes. This will be achieved by assigning...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1006/mben.2000.0175

    authors: Kremling A,Gilles ED

    更新日期:2001-04-01 00:00:00

  • A modular autoinduction device for control of gene expression in Bacillus subtilis.

    abstract::Intense synthesis of proteins and chemicals in engineered microbes impose metabolic burden, frequently leading to reduced growth and heterogeneous cell population. Thus, the correct balance between growth and production is important. Such balance can be engineered through dynamic control of pathways, but few broadly a...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2020.03.012

    authors: Corrêa GG,Lins MRDCR,Silva BF,de Paiva GB,Zocca VFB,Ribeiro NV,Picheli FP,Mack M,Pedrolli DB

    更新日期:2020-09-01 00:00:00

  • Isobutanol and 2-ketoisovalerate production by Klebsiella pneumoniae via a native pathway.

    abstract::Isobutanol is a valuable chemical and is considered a new generation biofuel. Construction of isobutanol synthesis pathways in bacteria is a hot topic in isobutanol production. Here, we show that an isobutanol synthesis pathway exists naturally in Klebsiella pneumoniae; however, this pathway is dormant in the wild-typ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2017.07.003

    authors: Gu J,Zhou J,Zhang Z,Kim CH,Jiang B,Shi J,Hao J

    更新日期:2017-09-01 00:00:00

  • Streptomyces species: Ideal chassis for natural product discovery and overproduction.

    abstract::There is considerable interest in mining organisms for new natural products (NPs) and in improving methods to overproduce valuable NPs. Because of the rapid development of tools and strategies for metabolic engineering and the markedly increased knowledge of the biosynthetic pathways and genetics of NP-producing organ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章,评审

    doi:10.1016/j.ymben.2018.05.015

    authors: Liu R,Deng Z,Liu T

    更新日期:2018-11-01 00:00:00

  • Metabolic engineering of Escherichia coli for the production of 5-aminovalerate and glutarate as C5 platform chemicals.

    abstract::5-Aminovalerate (5AVA) is the precursor of valerolactam, a potential building block for producing nylon 5, and is a C5 platform chemical for synthesizing 5-hydroxyvalerate, glutarate, and 1,5-pentanediol. Escherichia coli was metabolically engineered for the production of 5-aminovalerate (5AVA) and glutarate. When the...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2012.11.011

    authors: Park SJ,Kim EY,Noh W,Park HM,Oh YH,Lee SH,Song BK,Jegal J,Lee SY

    更新日期:2013-03-01 00:00:00

  • Human 293 cell metabolism in low glutamine-supplied culture: interpretation of metabolic changes through metabolic flux analysis.

    abstract::Metabolic flux analysis is a useful tool to analyze cell metabolism. In this study, we report the use of a metabolic model with 34 fluxes to study the 293 cell, in order to improve its growth capacity in a DMEM/F12 medium. A batch, fed-batch with glutamine feeding, fed-batch with essential amino acids, and finally a f...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1006/mben.2000.0152

    authors: Nadeau I,Sabatié J,Koehl M,Perrier M,Kamen A

    更新日期:2000-10-01 00:00:00

  • Down-regulation of cold-inducible RNA-binding protein does not improve hypothermic growth of Chinese hamster ovary cells producing erythropoietin.

    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

    authors: Hong JK,Kim YG,Yoon SK,Lee GM

    更新日期:2007-03-01 00:00:00

  • Understanding carotenoid metabolism as a necessity for genetic engineering of crop plants.

    abstract::As a proof of concept, the qualitative and quantitative engineering of carotenoid formation has been achieved in crop plants. Successful reports in tomato, potato, rice, and canola all describe the enhancement of carotenoid with nutritional value, while in model systems such as tobacco and Arabidopsis the engineering ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章,评审

    doi:10.1016/j.ymben.2006.01.005

    authors: Sandmann G,Römer S,Fraser PD

    更新日期:2006-07-01 00:00:00

  • Identification of Absidia orchidis steroid 11β-hydroxylation system and its application in engineering Saccharomyces cerevisiae for one-step biotransformation to produce hydrocortisone.

    abstract::Hydrocortisone is an effective anti-inflammatory drug and also an important intermediate for synthesis of other steroid drugs. The filamentous fungus Absidia orchidis is renowned for biotransformation of acetylated cortexolone through 11β-hydroxylation to produce hydrocortisone. However, due to the presence of 11α-hyd...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2019.10.006

    authors: Chen J,Fan F,Qu G,Tang J,Xi Y,Bi C,Sun Z,Zhang X

    更新日期:2020-01-01 00:00:00

  • Identification and elimination of metabolic bottlenecks in the quinone modification pathway for enhanced coenzyme Q10 production in Rhodobacter sphaeroides.

    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

    authors: Lu W,Ye L,Lv X,Xie W,Gu J,Chen Z,Zhu Y,Li A,Yu H

    更新日期:2015-05-01 00:00:00

  • Ethyl acetate production by the elusive alcohol acetyltransferase from yeast.

    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

    authors: Kruis AJ,Levisson M,Mars AE,van der Ploeg M,Garcés Daza F,Ellena V,Kengen SWM,van der Oost J,Weusthuis RA

    更新日期:2017-05-01 00:00:00

  • High-yield whole cell biosynthesis of Nylon 12 monomer with self-sufficient supply of multiple cofactors.

    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

    authors: Ge J,Yang X,Yu H,Ye L

    更新日期:2020-11-01 00:00:00

  • Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors.

    abstract::Mutations in succinate dehydrogenase (SDH) are associated with tumor development and neurodegenerative diseases. Only in tumors, loss of SDH activity is accompanied with the loss of complex I activity. Yet, it remains unknown whether the metabolic phenotype of SDH mutant tumors is driven by loss of complex I function,...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2016.11.005

    authors: Lorendeau D,Rinaldi G,Boon R,Spincemaille P,Metzger K,Jäger C,Christen S,Dong X,Kuenen S,Voordeckers K,Verstreken P,Cassiman D,Vermeersch P,Verfaillie C,Hiller K,Fendt SM

    更新日期:2017-09-01 00:00:00

  • Metabolic engineering of Corynebacterium glutamicum for the de novo production of ethylene glycol from glucose.

    abstract::Development of sustainable biological process for the production of bulk chemicals from renewable feedstock is an important goal of white biotechnology. Ethylene glycol (EG) is a large-volume commodity chemical with an annual production of over 20 million tons, and it is currently produced exclusively by petrochemical...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2015.10.013

    authors: Chen Z,Huang J,Wu Y,Liu D

    更新日期:2016-01-01 00:00:00

  • Punicic acid production in Brassica napus.

    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

    authors: Xu Y,Mietkiewska E,Shah S,Weselake RJ,Chen G

    更新日期:2020-11-01 00:00:00

  • Overexpression of a novel endogenous NADH kinase in Aspergillus nidulans enhances growth.

    abstract::The complete genome sequence of the filamentous fungi Aspergillus nidulans has paved the way for fundamental research on this industrially important species. To the best of our knowledge, this is the first time a gene encoding for ATP-dependent NADH kinase (ATP:NADH 2'-phosphotransferase, EC 2.7.1.86) has been identif...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2008.08.008

    authors: Panagiotou G,Grotkjaer T,Hofmann G,Bapat PM,Olsson L

    更新日期:2009-01-01 00:00:00

  • Chromosome engineering of the TCA cycle in Halomonas bluephagenesis for production of copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV).

    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

    authors: Chen Y,Chen XY,Du HT,Zhang X,Ma YM,Chen JC,Ye JW,Jiang XR,Chen GQ

    更新日期:2019-07-01 00:00:00

  • Anaerobic production of medium-chain fatty alcohols via a β-reduction pathway.

    abstract::In this report, we identify the relevant factors to increase production of medium chain n-alcohols through an expanded view of the reverse β-oxidation pathway. We began by creating a base strain capable of producing medium chain n-alcohols from glucose using a redox-balanced and growth-coupled metabolic engineering st...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2018.05.011

    authors: Mehrer CR,Incha MR,Politz MC,Pfleger BF

    更新日期:2018-07-01 00:00:00

  • Recombinant strains for the enhanced production of bioengineered rapalogs.

    abstract::The rapK gene required for biosynthesis of the DHCHC starter acid that initiates rapamycin biosynthesis was deleted from strain BIOT-3410, a derivative of Streptomyces rapamycinicus which had been subjected to classical strain and process development and capable of robust rapamycin production at titres up to 250mg/L. ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2012.11.001

    authors: Kendrew SG,Petkovic H,Gaisser S,Ready SJ,Gregory MA,Coates NJ,Nur-E-Alam M,Warneck T,Suthar D,Foster TA,McDonald L,Schlingman G,Koehn FE,Skotnicki JS,Carter GT,Moss SJ,Zhang MQ,Martin CJ,Sheridan RM,Wilkinson B

    更新日期:2013-01-01 00:00:00

  • Engineering Escherichia coli to produce branched-chain fatty acids in high percentages.

    abstract::Branched-chain fatty acids (BCFAs) are key precursors of branched-chain fuels, which have cold-flow properties superior to straight chain fuels. BCFA production in Gram-negative bacterial hosts is inherently challenging because it competes directly with essential and efficient straight-chain fatty acid (SCFA) biosynth...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2016.07.003

    authors: Bentley GJ,Jiang W,Guamán LP,Xiao Y,Zhang F

    更新日期:2016-11-01 00:00:00

  • Efficient production of saffron crocins and picrocrocin in Nicotiana benthamiana using a virus-driven system.

    abstract::Crocins and picrocrocin are glycosylated apocarotenoids responsible, respectively, for the color and the unique taste of the saffron spice, known as red gold due to its high price. Several studies have also shown the health-promoting properties of these compounds. However, their high costs hamper the wide use of these...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2020.06.009

    authors: Martí M,Diretto G,Aragonés V,Frusciante S,Ahrazem O,Gómez-Gómez L,Daròs JA

    更新日期:2020-09-01 00:00:00

  • Systematic identification and elimination of flux bottlenecks in the aldehyde production pathway of Synechococcus elongatus PCC 7942.

    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

    authors: Cheah YE,Xu Y,Sacco SA,Babele PK,Zheng AO,Johnson CH,Young JD

    更新日期:2020-07-01 00:00:00

  • Efficient reduction of the formation of by-products and improvement of production yield of 2,3-butanediol by a combined deletion of alcohol dehydrogenase, acetate kinase-phosphotransacetylase, and lactate dehydrogenase genes in metabolically engineered Kl

    abstract::Klebsiella oxytoca KMS005 (∆adhE∆ackA-pta∆ldhA) was metabolically engineered to improve 2,3-butanediol (BDO) yield. Elimination of alcohol dehydrogenase E (adhE), acetate kinase A-phosphotransacetylase (ackA-pta), and lactate dehydrogenase A (ldhA) enzymes allowed BDO production as a primary pathway for NADH re-oxidat...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2015.04.004

    authors: Jantama K,Polyiam P,Khunnonkwao P,Chan S,Sangproo M,Khor K,Jantama SS,Kanchanatawee S

    更新日期:2015-07-01 00:00:00

  • Metabolic design for selective production of nicotinamide mononucleotide from glucose and nicotinamide.

    abstract::β-Nicotinamide mononucleotide (NMN) is, one of the nucleotide compounds, a precursor of NAD+ and has recently attracted attention as a nutraceutical. Here, we develop a whole-cell biocatalyst using Escherichia coli, which enabled selective and effective high production of NMN from the inexpensive feedstock substrates ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2020.11.008

    authors: Shoji S,Yamaji T,Makino H,Ishii J,Kondo A

    更新日期:2020-11-18 00:00:00

  • Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis.

    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

    authors: Rodriguez A,Kildegaard KR,Li M,Borodina I,Nielsen J

    更新日期:2015-09-01 00:00:00

  • Metabolic engineering of Amycolatopsis japonicum for optimized production of [S,S]-EDDS, a biodegradable chelator.

    abstract::The actinomycete Amycolatopsis japonicum is the producer of the chelating compound [S,S]-ethylenediamine-disuccinc acid (EDDS). [S,S]-EDDS is an isomer of ethylenediamine-tetraacetic acid (EDTA), an economically important chelating compound that suffers from an extremely poor degradability. Frequent use of the persist...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2020.04.003

    authors: Edenhart S,Denneler M,Spohn M,Doskocil E,Kavšček M,Amon T,Kosec G,Smole J,Bardl B,Biermann M,Roth M,Wohlleben W,Stegmann E

    更新日期:2020-07-01 00:00:00

  • Metabolic engineering of aerobic succinate production systems in Escherichia coli to improve process productivity and achieve the maximum theoretical succinate yield.

    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

    authors: Lin H,Bennett GN,San KY

    更新日期:2005-03-01 00:00:00

  • Improving recombinant bone morphogenetic protein-4 (BMP-4) production by autoregulatory feedback loop removal using BMP receptor-knockout CHO cell lines.

    abstract::A Chinese hamster ovary (CHO) cell line producing recombinant human bone morphogenetic protein-4 (rhBMP-4) (CHO-BMP-4), which expresses essential components of BMP signal transduction, underwent autocrine BMP-4 signaling. RNA seq analysis on CHO host cells (DG44) treated with rhBMP-4 (20 µg/mL) suggested that rhBMP-4 ...

    journal_title:Metabolic engineering

    pub_type: 杂志文章

    doi:10.1016/j.ymben.2018.11.003

    authors: Kim CL,Lee GM

    更新日期:2019-03-01 00:00:00