Abstract：
:This review concerns the issues involved in the industrial development of fed-batch culture processes with Saccharomyces cerevisiae strains producing heterologous proteins. Most of process development considerations with fed-batch recombinant cultures are linked to the reliability and reproducibility of the process for manufacturing environments where quality assurance and quality control aspects are paramount. In this respect, the quality, safety and efficacy of complex biologically active molecules produced by recombinant techniques are strongly influenced by the genetic background of the host strain, genetic stability of the transformed strain and production process factors. An overview of the recent literature of these culture-related factors is coupled with our experience in yeast fed-batch process development for producing various therapeutic grade proteins. The discussion is based around three principal topics: genetics, microbial physiology and fed-batch process design. It includes the fundamental aspects of yeast strain physiology, the nature of the recombinant product, quality control aspects of the biological product, features of yeast expression vectors, expression and localization of recombinant products in transformed cells and fed-batch process considerations for the industrial production of Saccharomyces cerevisiae recombinant proteins. It is our purpose that this review will provide a comprehensive understanding of the fed-batch recombinant production processes and challenges commonly encountered during process development.
journal_name
FEMS Microbiol Revjournal_title
FEMS microbiology reviewsauthors
Mendoza-Vega O,Sabatié J,Brown SWdoi
10.1111/j.1574-6976.1994.tb00146.xsubject
Has Abstractpub_date
1994-12-01 00:00:00pages
369-410issue
4eissn
0168-6445issn
1574-6976journal_volume
15pub_type
杂志文章,评审abstract：:Respiratory syncytial virus is the major respiratory pathogen of infants and children worldwide, with no effective treatment or vaccine available. Steady progress has been made in understanding the respiratory syncytial virus life cycle and the consequences of infection, but many areas of respiratory syncytial virus b...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2006.00025.x
更新日期：2006-09-01 00:00:00
abstract：:Hydrophobins are surface active proteins produced by filamentous fungi. They have a role in fungal growth as structural components and in the interaction of fungi with their environment. They have, for example, been found to be important for aerial growth, and for the attachment of fungi to solid supports. Hydrophobin...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1016/j.femsre.2005.01.004
更新日期：2005-11-01 00:00:00
abstract：:Methanogens form a very large and diverse group of microorganisms within the domain of the Archaea. Energy for their growth is obtained by the reduction of a variety of substrates into methane. Several genes, coding for enzymes involved in methanogenesis or in the central metabolism have been cloned and studied. The m...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.1994.tb00138.x
更新日期：1994-10-01 00:00:00
abstract：:Purine salvage is an essential function for all obligate parasitic protozoa studied to date and most are also capable of efficient uptake of preformed pyrimidines. Much progress has been made in the identification and characterisation of protozoan purine and pyrimidine transporters. While the genes encoding protozoan ...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1016/j.femsre.2005.03.004
更新日期：2005-11-01 00:00:00
abstract：:Meningococcal disease is a serious and rapidly progressing illness. It is therefore very important to monitor changes in the level of antibiotic susceptibility among clinical isolates. Different aspects such as interpretation of laboratory results, determination of breakpoints predicting treatment failure as well as d...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2006.00049.x
更新日期：2007-01-01 00:00:00
abstract：:Thioredoxin is a small (Mr 12,000) ubiquitous redox protein with the conserved active site structure: -Trp-Cys-Gly-Pro-Cys-. The oxidized form (Trx-S2) contains a disulfide bridge which is reduced by NADPH and thioredoxin reductase; the reduced form [Trx(SH)2] is a powerful protein disulfide oxidoreductase. Thioredoxi...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6968.1988.tb02747.x
更新日期：1988-12-01 00:00:00
abstract：:The initiation of transcription is the most important step for gene regulation in eubacteria. To initiate transcription, RNA polymerase has to associate with a small protein, known as a sigma-factor. The sigma-factor directs RNA polymerase to a specific class of promoter sequences. Most bacterial species synthesize se...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.1998.tb00364.x
更新日期：1998-09-01 00:00:00
abstract：:N-Substituted aromatic compounds are environmental contaminants associated with the production and use of dyes, explosives, pesticides and pharmaceuticals. In this article, we examine the potential of anaerobic granular sludge from anaerobic treatment systems towards the detoxification, transformation, and mineralizat...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章
doi：10.1111/j.1574-6976.1997.tb00335.x
更新日期：1997-07-01 00:00:00
abstract：:Glucuronide and sulfate conjugation are important pathways in the peripheral metabolism of thyroid hormone. These reactions occur predominantly in the liver, and especially the glucuronides are excreted in the bile. Although an enterohepatic circulation after intestinal hydrolysis of iodothyronine conjugates is sugges...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6968.1988.tb02709.x-i1
更新日期：1988-02-01 00:00:00
abstract：:A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor samples of patients with different malignancies is now well documented, although the causative role for HCMV in the development of the neoplasias remains to be established. HCMV infection can modulate multiple cellular regulatory and signall...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1016/j.femsre.2003.07.005
更新日期：2004-02-01 00:00:00
abstract：:A close symbiotic relationship exists between the intestinal microbiota and its host. A critical component of gut homeostasis is the presence of a mucus layer covering the gastrointestinal tract. Mucus is a viscoelastic gel at the interface between the luminal content and the host tissue that provides a habitat to the...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fuz013
更新日期：2019-09-01 00:00:00
abstract：:Pseudomonas putida is a gram-negative rod-shaped gammaproteobacterium that is found throughout various environments. Members of the species P. putida show a diverse spectrum of metabolic activities, which is indicative of their adaptation to various niches, which includes the ability to live in soils and sediments con...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2010.00249.x
更新日期：2011-03-01 00:00:00
abstract：:Sequencing-based studies have illuminated increased transcriptional complexity within the genome structure of bacteria and have resulted in the identification of many small regulatory RNAs (sRNA) and a large amount of antisense transcription. It remains an open question whether these sRNAs all indeed play regulatory r...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fuv022
更新日期：2015-05-01 00:00:00
abstract：:Five species of parasite cause malaria in humans with the most severe disease caused by Plasmodium falciparum. Many of the proteins encoded in the P. falciparum genome are unusually enriched in repetitive low-complexity sequences containing a limited repertoire of amino acids. These repetitive sequences expand and con...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fux046
更新日期：2017-11-01 00:00:00
abstract：:In recent years, there has been accumulating evidence that antibiotics, besides their antimicrobial action, potentially have a number of undesired side effects that can, at least in some cases, promote genetic variability of bacteria. In addition to resistant variants, antibiotics have also been shown to select mutato...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2009.00165.x
更新日期：2009-05-01 00:00:00
abstract：:Arsenic compounds have been abundant at near toxic levels in the environment since the origin of life. In response, microbes have evolved mechanisms for arsenic resistance and enzymes that oxidize As(III) to As(V) or reduce As(V) to As(III). Formation and degradation of organoarsenicals, for example methylarsenic comp...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2002.tb00617.x
更新日期：2002-08-01 00:00:00
abstract：:Type II (proteic) toxin-antitoxin (TA) operons are widely spread in bacteria and archaea. They are organized as operons in which, usually, the antitoxin gene precedes the cognate toxin gene. The antitoxin generally acts as a transcriptional self-repressor, whereas the toxin acts as a co-repressor, both proteins consti...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fuv002
更新日期：2015-07-01 00:00:00
abstract：:Cyanobacteria of the genera Synechococcus and Prochlorococcus dominate the prokaryotic component of the picophytoplankton in the oceans. It is still less than 10 years since the discovery of phages that infect marine Synechococcus and the beginning of the characterisation of these phages and assessment of their ecolog...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1016/S0168-6445(03)00016-0
更新日期：2003-04-01 00:00:00
abstract：:Ribonuclease P is the endonuclease required for generating the mature tRNA 5'-end. The ribonucleoprotein character of this enzyme has now been proven in most organisms and organelles. Exceptions, however, are still the chloroplasts, plant nuclei and animal mitochondria where no associated RNAs have been detected to da...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.1999.tb00406.x
更新日期：1999-06-01 00:00:00
abstract：:DNA microarrays are a powerful and promising approach to gain a detailed understanding of the bacterial response and the molecular cross-talk that can occur as a consequence of host-pathogen interactions. However, published studies mainly describe the host response to infection. Analysis of bacterial gene regulation i...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2008.00103.x
更新日期：2008-05-01 00:00:00
abstract：:Research innovations are constantly occurring in universities, research institutions and industrial research laboratories. These are reported in the scientific literature and presented to the scientific community in various congresses and symposia as well as through direct contacts and collaborations. Conversion of th...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1016/j.femsre.2005.04.001
更新日期：2005-08-01 00:00:00
abstract：:The production of the fusion protein staphylococcal protein A/E. coli beta-galactosidase in Escherichia coli was studied in batch and fed batch cultivations. Batch cultivation of a recombinant E. coli strain yielded a final cell dry weight of 16.4 g l-1 with a final intracellular product concentration of recombinant p...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章
doi：10.1111/j.1574-6976.1994.tb00072.x
更新日期：1994-05-01 00:00:00
abstract：:Microbial networks are an increasingly popular tool to investigate microbial community structure, as they integrate multiple types of information and may represent systems-level behaviour. Interpreting these networks is not straightforward, and the biological implications of network properties are unclear. Analysis of...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fuy030
更新日期：2018-11-01 00:00:00
abstract：:Dengue is the most prevalent arthropod-borne viral disease, caused by dengue virus, a member of the Flaviviridae family. Its worldwide incidence is now a major health problem, with 2.5 billion people living in risk areas. In this review, we integrate the structural rearrangements of each viral protein and their functi...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fuu004
更新日期：2015-03-01 00:00:00
abstract：:Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically for long periods of time and pose significant public-health problems. Multidrug-resistant S. enterica serovar Typhi (S. Typhi) and nontyphoidal Salmonella (NTS) are on the increase and are often associate...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2012.00332.x
更新日期：2012-05-01 00:00:00
abstract：:First insights on the human gut microbiome have been gained from medium-sized, cross-sectional studies. However, given the modest portion of explained variance of currently identified covariates and the small effect size of gut microbiota modulation strategies, upscaling seems essential for further discovery and chara...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fux027
更新日期：2017-08-01 00:00:00
abstract：:Heat-shock proteins (hsps) have been identified as molecular chaperones conserved between microbes and man and grouped by their molecular mass and high degree of amino acid homology. This article reviews the major hsps of Saccharomyces cerevisiae, their interactions with trehalose, the effect of fermentation and the r...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2005.00001.x
更新日期：2006-01-01 00:00:00
abstract：:More than a century ago, the term 'virus' was introduced to describe infectious agents that are invisible by light microscopy and capable of passing through sterilizing filters. In addition to their extremely small size, most viruses have minimal genomes and gene contents, and rely almost entirely on host cell-encoded...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1093/femsre/fuv037
更新日期：2015-11-01 00:00:00
abstract：:Quinolone-resistant Salmonella enterica usually contain a mutation in gyrA within the region encoding the quinolone resistance determining region of the A subunit of DNA gyrase. These mutations confer substitutions analogous to Escherichia coli Ser83-->Phe and Asp87-->Gly or Tyr, or a novel mutation resulting in Ala11...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章
doi：10.1111/j.1574-6976.2002.tb00596.x
更新日期：2002-03-01 00:00:00
abstract：:It has become increasingly and widely recognised that bacteria do not exist as solitary cells, but are colonial organisms that exploit elaborate systems of intercellular communication to facilitate their adaptation to changing environmental conditions. The languages by which bacteria communicate take the form of chemi...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1574-6976.2001.tb00583.x
更新日期：2001-08-01 00:00:00
