Biotin formation by recombinant strains of Escherichia coli: influence of the host physiology

Sabatié, J.; Speck, Denis; Reymund, Jacqueline; Hebert, C. Nancy; Caussin, L.; Weltin, D.; Gloeckler, R.; O’Regan, Michael H.; Bernard, S.; Ledoux, Catherine; Ohsawa, I.; Kamogawa, K.; Lemoine, Yves; Brown, Stephen

doi:10.1016/0168-1656(91)90033-r

Cited by 22 publications

(12 citation statements)

References 16 publications

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“…Until now, recombinant DNA technology has been used to add straightforward conversion pathways which produce new and desirable cellular functions. For instance, E. coli strains producing biotin (Sabatie et al, 1991) and indigo (Ensley, 1985) were designed by introducing foreign genes obtained directly from the biotin and indigo production pathways of Bacillus sphaericus and Pseudomonas putida, respectively. Other success stories include enhancing E. coli's ability to overexpress heterologous proteins (Aristidou et al, 1994;Chou et al, 1994;Dedhia et al, 1994) and engineering microorganisms to biodegrade pollutants such as heavy metals , phosphates Van Dien and Keasling, 1998), and trichloroethylene (Winter et al, 1989).…”

Section: Background and Objectivesmentioning

confidence: 99%

Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions

Burgard

Maranas

2001

Biotech & Bioengineering

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An optimization-based procedure for studying the response of metabolic networks after gene knockouts or additions is introduced and applied to a linear flux balance analysis (FBA) Escherichia coli model. Both the gene addition problem of optimally selecting which foreign genes to recombine into E. coli, as well as the gene deletion problem of removing a given number of existing ones, are formulated as mixed-integer optimization problems using binary 0-1 variables. The developed modeling and optimization framework is tested by investigating the effect of gene deletions on biomass production and addressing the maximum theoretical production of the 20 amino acids for aerobic growth on glucose and acetate substrates. In the gene deletion study, the smallest gene set necessary to achieve maximum biomass production in E. coli is determined for aerobic growth on glucose. The subsequent gene knockout analysis indicates that biomass production decreases monotonically, rendering the metabolic network incapable of growth after only 18 gene deletions. In the gene addition study, the E. coli flux balance model is augmented with 3,400 non-E. coli reactions from the KEGG database to form a multispecies model. This model is referred to as the Universal model. This study reveals that the maximum theoretical production of six amino acids could be improved by the addition of only one or two genes to the native amino acid production pathway of E. coli, even though the model could choose from 3,400 foreign reaction candidates. Specifically, manipulation of the arginine production pathway showed the most promise with 8.75% and 9.05% predicted increases with the addition of genes for growth on glucose and acetate, respectively. The mechanism of all suggested enhancements is either by: 1) improving the energy efficiency and/or 2) increasing the carbon conversion efficiency of the production route.

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Section: Background and Objectivesmentioning

confidence: 99%

Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions

Burgard

Maranas

2001

Biotech & Bioengineering

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“…Several reports indicate the limitation of carbon, nitrogen and phosphate can be detrimental to plasmid stability [95][96][97]. The nature of complex nitrogen sources could also influence the segregrational stability and the metabolic flux to the production of the recombinant protein [98]. Although our yeast expression systems using 2 /xm-based plasmids have shown a high plasmid stability under different culture conditions, some authors have reported a plasmid segregational instability employing 2 /xm-based chimeric plasmids under different culture media and dissolved oxygen concentrations [99,100].…”

Section: Nature Of the Yeast Expression Cectorsmentioning

confidence: 99%

Industrial production of heterologous proteins by fed-batch cultures of the yeast Saccharomyces cereuisiae

Mendoza-Vega

1994

FEMS Microbiology Reviews

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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.

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“…These strains also contain bioW [coding for PmCoA synthetase (Gloeckler et al 1990)] and the bioY, and bioX genes (unknown functions) and were cultivated in the presence of pimelic acid. Furthermore, Sabati6 et al (1991) recently reported that their strains synthesized a BioB protein that is mostly insoluble (>95%0), which could account for the bottleneck the authors found between DTB and biotin.…”

Section: Discussionmentioning

confidence: 99%

“…Since biotin is passively excreted (Piffeteau and Gaudry 1985), we, like Sabati6 et al (1991), assumed that appreciable amounts of vitamers would not accumulate intracellularly. Since biotin is passively excreted (Piffeteau and Gaudry 1985), we, like Sabati6 et al (1991), assumed that appreciable amounts of vitamers would not accumulate intracellularly.…”

Section: Vitamer Accumulation and Enzyme Activitiesmentioning

confidence: 99%

Biotin biosynthetic pathway in recombinant strains of Escherichia coli overexpressing bio genes: evidence for a limiting step upstream from KAPA

Lévy-Schil¹,

Debussche

Rigault³

et al. 1993

Appl Microbiol Biotechnol

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The effect of the overexpression of the bioABFCD operon on the biotin biosynthetic pathway was investigated in an Escherichia coli K12 bioR mutant B ioC,Bi oH with a chromosomal deletion for the biotin operon. When transformed with a multicopy number plasmid NH2 J containing bioABFCD, this strain synthesized 10,000CH~-CH-C00H + times more biotin than a wild-type E. coli strain. In or-BioF der to further increase biotin production, the bioA and bioB operons were subcloned into plasmids with stronger promoters and in some cases optimal ribosome binding sites. The new constructions led to the accumulation of large amounts of soluble Bio proteins (although not BioA BioC) but did not improve biotin production. In all the constructed strains, BioA, BioD, and BioB activities were greatly amplified but these activities did not correlate with the level of protein synthesis. These strains ac-B i o O cumulated only low levels of vitamers, suggesting that the major limiting step for higher biotin production occurs upstream from the first intermediate of the Bio pathway we assayed (7,keto-8-aminopelargonic acid). As BioC overproduction was shown to impair cell growth, we could not determine if this early step of the pathway was limiting.

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Biotin formation by recombinant strains of Escherichia coli: influence of the host physiology

Cited by 22 publications

References 16 publications

Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions

Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions

Industrial production of heterologous proteins by fed-batch cultures of the yeast Saccharomyces cereuisiae

Biotin biosynthetic pathway in recombinant strains of Escherichia coli overexpressing bio genes: evidence for a limiting step upstream from KAPA

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