Increased heterologous protein production by Saccharomyces cerevisiae growing on ethanol as sole carbon source.

Abstract:

:Saccharomyces cerevisiae is a widely used host organism for the production of heterologous proteins, often cultivated in glucose-based fed-batch processes. This production system however has many factors limiting the productivity, mainly towards the end of the fermentation. For the optimised production of a Camelid antibody fragment this process was evaluated. In shake flask cultivations, it was found that ethanol has a strong effect on productivity increase and therefore glucose and ethanol fed-batch fermentations were compared. It appeared that specific heterologous protein production was up to five times higher in the ethanol cultivation and could be further optimised. Then the key characteristics of ethanol fed-batch fermentations such as growth rate and specific production were determined under ethanol limitation and accumulation and growth limiting conditions in the final phase of the process. It appeared that an optimal production process should have an ethanol accumulation throughout the feed phase of approximately 1% v/v in the broth and that production remains very efficient even in the last phase of the process. This productivity increase on ethanol versus glucose was also proven for several other Camelid antibody fragments some of which were heavily impaired in secretion on glucose, but very well produced on ethanol. This leads to the suggestion that the ethanol effect on improved heterologous protein production is linked to a stress response and folding and secretion efficiency.

journal_name

Biotechnol Bioeng

authors

van de Laar T,Visser C,Holster M,López CG,Kreuning D,Sierkstra L,Lindner N,Verrips T

doi

10.1002/bit.21150

subject

Has Abstract

pub_date

2007-02-15 00:00:00

pages

483-94

issue

3

eissn

0006-3592

issn

1097-0290

journal_volume

96

pub_type

杂志文章
  • A study of D-lactate and extracellular methylglyoxal production in lactate re-utilizing CHO cultures.

    abstract::In large-scale mammalian cell culture, the key toxic by-products assessed and monitored are lactate and ammonia. Often no distinction between the two isoforms of lactate is made. Here, we present profiles of both D- and L-lactate. D-Lactate is the end molecule of the methylglyoxal pathway. D-Lactate unlike L-lactate i...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22757

    authors: Paoli T,Faulkner J,O'kennedy R,Keshavarz-Moore E

    更新日期:2010-09-01 00:00:00

  • On the enthalpy of formation of Escherichia coli K-12 cells.

    abstract::An examination is made of five methods for obtaining values of the enthalpy of formation of a unit mass of living Escherichia coli K-12 cells. The values obtained by these methods ranged from -88.95 kJ to -99.55 kJ, the gross average being 96.01 kJ, per unit carbon formula weight equivalent of living, hydrated cells. ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260390103

    authors: Battley EH

    更新日期:1992-01-05 00:00:00

  • Model for on-line moisture-content control during solid-state fermentation.

    abstract::In this study we describe a model that estimates the extracellular (nonfungal) and overall water contents of wheat grains during solid-state fermentation (SSF) with Aspergillus oryzae, using on-line measurements of oxygen, carbon dioxide, and water vapor in the gas phase. The model uses elemental balances to predict s...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/1097-0290(20000120)72:2<231::aid-bit11>3.0

    authors: Nagel FJ,Tramper J,Bakker MS,Rinzema A

    更新日期:2001-01-20 00:00:00

  • Model analysis of biological oxygen transfer enhancement in surface-aerated bioreactors.

    abstract::A model was developed to evaluate the effects of cells and surfactants on oxygen transfer in surface-aerated bioreactors. The model assumed the presence of serial layers of adsorbed surfactants and microorganisms directly adjacent to the gas-liquid interface due to their surface activities, followed by a stagnant liqu...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260401108

    authors: Ju LK,Sundarajan A

    更新日期:1992-12-20 00:00:00

  • CRISPR interference of nucleotide biosynthesis improves production of a single-domain antibody in Escherichia coli.

    abstract::Growth decoupling can be used to optimize the production of biochemicals and proteins in cell factories. Inhibition of excess biomass formation allows for carbon to be utilized efficiently for product formation instead of growth, resulting in increased product yields and titers. Here, we used CRISPR interference to in...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.27536

    authors: Landberg J,Wright NR,Wulff T,Herrgård MJ,Nielsen AT

    更新日期:2020-08-18 00:00:00

  • Control of the redox potential by oxygen limitation improves bacterial leaching of chalcopyrite.

    abstract::Shake flask and stirred tank bioleaching experiments showed that the dissolution of chalcopyrite is inhibited by ferric ion concentrations as low as 200 mg L(-1) and redox potentials >420 mV (vs. Ag/AgCl). Chemical leaching of chalcopyrite (4% suspension, surface area 2.3 m2 g(-1)) was enhanced fourfold in the presenc...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.10184

    authors: Third KA,Cord-Ruwisch R,Watling HR

    更新日期:2002-05-20 00:00:00

  • Plasmid stability in budding yeast populations: Steady-state growth with selection pressure.

    abstract::Plasmid gene product accumulation in a cell population depends on the fraction of plasmid-containing cells and the distribution of single-cell plasmid content. These important population properties have been related to plasmid replication regulation and kinetics and to plasmid segregation rules at the single-cell leve...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260260519

    authors: Hjortso MA,Bailey JE

    更新日期:1984-05-01 00:00:00

  • Engineered cell migration to lesions linked to autoimmune disease.

    abstract::The damaging and degenerative effects in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease often manifests as the formation of lesions that feature a high local concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF along with other pro-inflammatory fa...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.26523

    authors: Mosabbir AA,Qudrat A,Truong K

    更新日期:2018-04-01 00:00:00

  • Simple constrained-optimization view of acetate overflow in E. coli.

    abstract::The production of acetate by aerobically growing E. coli is examined. The problem is formulated in terms of a flow network that has as its objective maximal ATP synthesis. It is found that when loads are imposed and flux constraints exist either at the level of NADH turnover rate or the activity of a key Krebs cycle e...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260350711

    authors: Majewski RA,Domach MM

    更新日期:1990-03-25 00:00:00

  • Immobilized enzyme cellulose hollow fibers: II. Kinetic analysis.

    abstract::Immobilized enzyme hollow fibers may be useful in the purification or treatment of whole blood under clinical conditions. In this study, catalytically pure heparinase was immobilized to cellulose to analyze the feasibility for the removal of heparin's anticoagulant activity from whole blood. The kinetics of catalytica...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260341105

    authors: Comfort AR,Albert E,Langer R

    更新日期:1989-12-20 00:00:00

  • Directed evolution of xylose specific transporters to facilitate glucose-xylose co-utilization.

    abstract::A highly active xylose specific transporter without glucose inhibition is highly desirable in cost-effective production of biofuels from lignocellulosic biomass. However, currently available xylose specific transporters suffer from low overall activity and most are inhibited by glucose. In this study, we applied a dir...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.25724

    authors: Wang M,Yu C,Zhao H

    更新日期:2016-03-01 00:00:00

  • Effects of mixing intensity on tissue-engineered cartilage.

    abstract::Mechanical forces regulate the structure and function of many tissues in vivo; recent results indicate that the mechanical environment can decisively influence the development of engineered tissues cultured in vitro. To investigate the effects of the hydrodynamic environment on tissue-engineered cartilage, primary bov...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/1097-0290(20000220)72:4<402::aid-bit1002>3

    authors: Gooch KJ,Kwon JH,Blunk T,Langer R,Freed LE,Vunjak-Novakovic G

    更新日期:2001-02-20 00:00:00

  • A flow-cytometric analysis of hybridoma growth and monoclonal antibody production.

    abstract::A flow cytometric kinetic study of hybridoma growth and monoclonal antibody production is presented, along with the influence of glutamine on intracellular responses such as (relative) cell size, and cell RNA and total protein content. Specific findings are: (1) RNA content remained constant throughout the growth phas...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260360109

    authors: Dalili M,Ollis DF

    更新日期:1990-06-05 00:00:00

  • Recombinant enterokinase light chain with affinity tag: expression from Saccharomyces cerevisiae and its utilities in fusion protein technology.

    abstract::Enterokinase and recombinant enterokinase light chain (rEK(L)) have been used widely to cleave fusion proteins with the target sequence of (Asp)(4)-Lys. In this work, we show that their utility as a site-specific cleavage agent is compromised by sporadic cleavage at other sites, albeit at low levels. Further degradati...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.10082

    authors: Choi SI,Song HW,Moon JW,Seong BL

    更新日期:2001-12-20 00:00:00

  • Concentration of baboon endogenous virus in large-scale production by use of hollow-fiber ultrafiltration technology.

    abstract::A process is described in which the baboon endogenous virus (BaEV) is produced under optimum conditions in cell culture, and concentrated by hollow-fiber ultrafiltration technology under conditions of large-scale production. This system has advantages over conventional systems in that the flow rate is increased 2.5-fo...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260220103

    authors: Weiss SA

    更新日期:1980-01-01 00:00:00

  • Tissue-engineering approaches in pancreatic islet transplantation.

    abstract::Pancreatic islet transplantation is a promising alternative to whole-pancreas transplantation as a treatment of type 1 diabetes mellitus. This technique has been extensively developed during the past few years, with the main purpose of minimizing the complications arising from the standard protocols used in organ tran...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章,评审

    doi:10.1002/bit.26821

    authors: Perez-Basterrechea M,Esteban MM,Vega JA,Obaya AJ

    更新日期:2018-12-01 00:00:00

  • Interspecific interactions in a methane-utilizing mixed culture.

    abstract::A two-member methane-utilizing mixed culture of bacteria, formed by combining two pure cultures isolated from a naturally occurring methane-utilizing mixed culture, was studied in continuous culture. From the nutritional requirements and substrate ranges of the pure cultures, a mechanism for the interspecific interact...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260221010

    authors: Lamb SC,Garver JC

    更新日期:1980-10-01 00:00:00

  • Egr1 and Gas6 facilitate the adaptation of HEK-293 cells to serum-free media by conferring enhanced viability and higher growth rates.

    abstract::Animal-derived serum is an essential media supplement for mammalian cells in cell culture. For a number of reasons including cost, regulatory concerns, lot inconsistency, potential contamination with adventitious agents, and down-stream processing it is desirable to eliminate the use of serum. Existing protocols desig...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.21707

    authors: Jaluria P,Konstantopoulos K,Betenbaugh M,Shiloach J

    更新日期:2008-04-15 00:00:00

  • Development of a novel adenovirus purification process utilizing selective precipitation of cellular DNA.

    abstract::The use of recombinant adenoviral vectors for vaccination and gene therapy requires the development of purification processes that are cost-effective, scalable, and capable of robust host cell DNA clearance. An adenovirus purification process was developed which incorporates selective precipitation of host cell DNA, e...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20406

    authors: Goerke AR,To BC,Lee AL,Sagar SL,Konz JO

    更新日期:2005-07-05 00:00:00

  • Reactive oxygen species induced by shear stress mediate cell death in Bacillus subtilis.

    abstract::Exposure of Bacillus subtilis to a shear rate of 1,482/s leads to a rapid loss of cell viability after 10 h of growth. Biochemical and molecular evidences provided below strongly suggest that cell death under high shear results from an apoptosis-like process similar to that described in eukaryotes, with activation of ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20835

    authors: Sahoo S,Rao KK,Suraishkumar GK

    更新日期:2006-05-05 00:00:00

  • Models for high cell density bioreactors must consider biomass volume fraction: Cell recycle example.

    abstract::Intrinsic models, which take into account biomass volume fraction, must be formulated for adequate simulation of high-biomass-density fermentations with cell recycle. Through comparison of corresponding intrinsic and non-intrinsic models in dimensionless form, constraints for non-intrinsic model usage in terms of biok...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260290906

    authors: Monbouquette HG

    更新日期:1987-06-01 00:00:00

  • Cell cycle progression in Escherichia coli B/r affects transcription of certain genes: Implications for synthetic genome design.

    abstract::We propose that transcript levels for some genes are affected by the bacterial cell division cycle and this may be an important factor to consider when designing synthetic bacterial genomes. To test this hypothesis, transcript levels of 58 genes in Escherichia coli B/r A were determined at five times during the cell d...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22098

    authors: Echtenkamp PL,Wilson DB,Shuler ML

    更新日期:2009-02-15 00:00:00

  • Fed-batch culture of Bacillus thuringiensis for thuringiensin production in a tower type bioreactor.

    abstract::Fed-batch culture of Bacillus thuringiensis in a modified airlift reactor has been developed by using adaptive control of glucose concentration in the reactor. The glucose concentration was estimated via a correlation equation between carbon dioxide production rate and glucose consumption rate. The estimated glucose c...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260480307

    authors: Jong JZ,Hsiun DY,Wu WT,Tzeng YM

    更新日期:1995-11-05 00:00:00

  • Coupling dark metabolism to electricity generation using photosynthetic cocultures.

    abstract::We investigated the role of green sulfur bacteria inlight-responsive electricity generation in microbial electrochemical cells (MXCs). We operated MXCs containing either monocultures or defined cocultures of previously enriched phototrophic Chlorobium and anode-respiring Geobacter under anaerobic conditions in the abs...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.25011

    authors: Badalamenti JP,Torres CI,Krajmalnik-Brown R

    更新日期:2014-02-01 00:00:00

  • Metabolic engineering of Escherichia coli for the production of 1,2-propanediol from glycerol.

    abstract::Due to its availability, low-price, and high degree of reduction, glycerol has become an attractive carbon source for the production of fuels and reduced chemicals. Using the platform we have established from the identification of key pathways mediating fermentative metabolism of glycerol, this work reports the engine...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22993

    authors: Clomburg JM,Gonzalez R

    更新日期:2011-04-01 00:00:00

  • Flotation of Streptomyces pilosus after lead accumulation.

    abstract::The flotation of Streptomyces pilosus was studied in the absence and presence of adsorbed Pb(II) ions on the cell walls and with and without using sodium dodecylsulfate (SDS) as collector. Adsorption of SDS onto the organism in the absence and presence of Pb(II) ions was also investigated. It was found that in the abs...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260371009

    authors: Sadowski Z,Golab Z,Smith RW

    更新日期:1991-04-25 00:00:00

  • Effects of culture conditions on N-glycolylneuraminic acid (Neu5Gc) content of a recombinant fusion protein produced in CHO cells.

    abstract::CHO cells express glycoproteins containing both the N-acetylneuraminic acid (Neu5Ac) and minor amounts of the N-glycolylneuraminic acid (Neu5Gc) forms of sialic acid. As Neu5Gc is not expressed in humans and can be recognized as a foreign epitope, there is the potential for immunogenicity issues for glycoprotein thera...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22644

    authors: Borys MC,Dalal NG,Abu-Absi NR,Khattak SF,Jing Y,Xing Z,Li ZJ

    更新日期:2010-04-15 00:00:00

  • Cell cycle model to describe animal cell size variation and lag between cell number and biomass dynamics.

    abstract::The use of cell numbers rather than mass to quantify the size of the biotic phase in animal cell cultures causes several problems. First, the cell size varies with growth conditions, thus yields expressed in terms of cell numbers cannot be used in the normal mass balance sense. Second, experience from microbial system...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0290(19971120)56:4<372::AID-BIT

    authors: Nielsen LK,Reid S,Greenfield PF

    更新日期:1997-11-20 00:00:00

  • Modeling brewers' yeast flocculation

    abstract::Flocculation of yeast cells occurs during the fermentation of beer. Partway through the fermentation the cells become flocculent and start to form flocs. If the environmental conditions, such as medium composition and fluid velocities in the tank, are optimal, the flocs will grow in size large enough to settle. After ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0290(19980205)57:3<330::aid-bit

    authors: van Hamersveld EH,van der Lans RG,Caulet PJ,Luyben KC

    更新日期:1998-02-05 00:00:00

  • Tetracycline-regulated overexpression of glycosyltransferases in Chinese hamster ovary cells.

    abstract::The glycosylation patterns of recombinant therapeutic glycoproteins can be engineered by overexpression of glycosyltransferases in the host cells used for glycoprotein production. Most prior glycosylation engineering experiments have involved constitutive expression of cloned glycosyltransferases. Here we use tetracyc...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:

    authors: Umaña P,Jean-Mairet J,Bailey JE

    更新日期:1999-12-05 00:00:00