References of "König, Ariane 50002126"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailThe credibility of expert advice for regulatory decision-making in the US and EU
König, Ariane UL; Jasanoff, Sheila

E-print/Working paper (2002)

Detailed reference viewed: 44 (5 UL)
Full Text
Peer Reviewed
See detailNegotiating the precautionary principle: Regulatory and institutional roots of divergent US and EU positions
König, Ariane UL

in International Journal of BioTechnology (2002), 4(1), 61-81

The precautionary principle has been a bone of contention in international negotiations on the governance of environmental and health risks. The US administration and European institutions often present ... [more ▼]

The precautionary principle has been a bone of contention in international negotiations on the governance of environmental and health risks. The US administration and European institutions often present opposing views on whether formal references to precaution help or hinder the global governance of risk, in particular where linked to world trade. The European Commission official position, backed by Council, Parliament and some Member States, advocates the principle's use in legal texts and pushes for the elaboration of international guidelines for its application. The proposed guidelines, whilst explicitly conforming to basic principles of trade law, include recommendations on broad socio-economic impact analyses of alternative risk mitigation measures and emphasise political aspects of decisions on risk. The US administration's official position papers oppose references to precaution and socio-economic impact analysis in international laws and guidelines on risk analysis. They mainly cite fears of abuse of the concept as guise for protectionist measures. In each administration a wide range of state and non-state actors with disparate views inform policy makers who then have to adopt one coherent position. This article suggests that overarching differences in the negotiating positions adopted by the US and European institutions, often attributed to culturally and politically rooted biases on risk and uncertainty, are also reflected in institutional practices and regulatory frameworks of the two jurisdictions. It recommends taking disparate institutional structures and regulatory frameworks into account in future deliberations on international guidelines on risk analysis. [less ▲]

Detailed reference viewed: 89 (5 UL)
Full Text
Peer Reviewed
See detailSafety considerations of DNA in food
Jonas, D. A.; Elmadfa, I.; Engel, K.-H. et al

in Annals of Nutrition & Metabolism (2001), 45(6), 1-20

Recombinant DNA techniques are capable of introducing genetic changes into food organisms that are more predictable than those introduced through conventional breeding techniques. This review discusses ... [more ▼]

Recombinant DNA techniques are capable of introducing genetic changes into food organisms that are more predictable than those introduced through conventional breeding techniques. This review discusses whether the consumption of DNA in approved novel foods and novel food ingredients derived from genetically modified organisms (GMOs) can be regarded as being as safe as the consumption of DNA in existing foods. It concludes that DNA from GMOs is equivalent to DNA from existing food organisms that has always been consumed with human diets. Any risks associated with the consumption of DNA will remain, irrespective of its origin, because the body handles all DNA in the same way. The breakdown of DNA during food processing and passage through the gastrointestinal tract reduces the likelihood that intact genes capable of encoding foreign proteins will be transferred to gut microflora. The review does not specifically address food safety issues arising from the consumption of viable genetically modified microorganisms but it shows that the likelihood of transfer and functional integration of DNA from ingested food by gut microflora and/or human cells is minimal. Information reviewed does not indicate any safety concerns associated with the ingestion of DNA per se from GMOs resulting from the use of currently available recombinant DNA techniques in the food chain. [less ▲]

Detailed reference viewed: 122 (5 UL)
Peer Reviewed
See detailTowards a common understanding of the precautionary principle?
König, Ariane UL

Article for general public (2000)

Detailed reference viewed: 79 (4 UL)
See detailDevelopment and biosafety aspects of transgene excision methods
König, Ariane UL

Scientific Conference (2000)

Detailed reference viewed: 29 (3 UL)
See detailRisk assessment of antibiotic resistance markers in genetically modified crops
König, Ariane UL

Scientific Conference (2000)

Detailed reference viewed: 154 (2 UL)
See detailGenetically modified crops in the European Union - the regulatory framework and public acceptance
König, Ariane UL

Scientific Conference (1998)

In both the United States and the European Union the fundamental concept for the food and environmental safety assessment of products derived from modern biotechnology is the concept of substantial ... [more ▼]

In both the United States and the European Union the fundamental concept for the food and environmental safety assessment of products derived from modern biotechnology is the concept of substantial equivalence, where the novel product is compared to a closely related product that has an accepted standard of safety. The concept was initially introduced by the World Health Organization (WHO) and the United Nations Food and Agricultural Organization (FAO) (WHO, 1991). In 1992, the Organisation for Economic Cooperation and Development (OECD) elaborated the underlying concept and introduced the term “substantial equivalence” (OECD, 1993). The application of substantial equivalence has since been reinforced by international expert bodies (WHO, 1995; FAO, 1996) and has been adopted by regulatory authorities in most countries. [less ▲]

Detailed reference viewed: 63 (5 UL)
Full Text
Peer Reviewed
See detailThe pipecolate-incorporating enzyme for the biosynthesis of the immunosuppressant rapamycin: Nucleotide sequence analysis, disruption and heterologous expression of rapP from Streptomyces hygroscopicus.
König, Ariane UL; Schwecke, T.; Molnár, I. et al

in European Journal of Biochemistry (1997), 247(2), 526-534

An open reading frame (rapP) encoding the putative pipecolate-incorporating enzyme (PIE) has been identified in the gene cluster for the biosynthesis of rapamycin in Streptomyces hygroscopicus. Conserved ... [more ▼]

An open reading frame (rapP) encoding the putative pipecolate-incorporating enzyme (PIE) has been identified in the gene cluster for the biosynthesis of rapamycin in Streptomyces hygroscopicus. Conserved amino acid sequence motifs for ATP binding, ATP hydrolysis, adenylate formation, and 4'-phosphopantetheine attachment were identified by sequence comparison with authentic peptide synthetases. Disruption of rapP by phage insertion abolished rapamycin production in S. hygroscopicus, and the production of the antibiotic was specifically restored upon loss of the inserted phage by a second recombination event. rapP was expressed in both Escherichia coli and Streptomyces coelicolor, and recombinant PIE was purified to homogeneity from both hosts. Although low-level incorporation of [14C]beta-alanine into recombinant PIE isolated from E. coli was detected, formation of the covalent acylenzyme intermediate could only be shown with the PIE from S. coelicolor, suggesting that while the recombinant PIE from S. coelicolor was phosphopantetheinylated, only a minor proportion of the recombinant enzyme from E. coli was post-translationally modified. [less ▲]

Detailed reference viewed: 83 (5 UL)
Full Text
See detailThe nature of the starter unit for the rapamycin polyketide synthase
König, Ariane UL; Schwecke, T.; Molnár, I. et al

in Angewandte Chemie International Edition (1996), 35(19), 2249-2251

A remarkably high level of incorporation is observed when 2,2,5,5-tetradeutero -3,4- dihydroxycyclo -hexanecarboxylic acid is fed to the rapamycin-producing organism. Intriguingly, however, analysis of ... [more ▼]

A remarkably high level of incorporation is observed when 2,2,5,5-tetradeutero -3,4- dihydroxycyclo -hexanecarboxylic acid is fed to the rapamycin-producing organism. Intriguingly, however, analysis of the gene sequence for the rapamycin polyketide synthase has suggested that the free acid may not normally be involved in rapamycin biosynthesis. [less ▲]

Detailed reference viewed: 83 (4 UL)
Full Text
Peer Reviewed
See detailOrganisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of the genes flanking the polyketide synthase
Aparicio, J. F.; Molnár, I.; Schwecke, T. et al

in Gene (1996), 169(1), 1-7

The three giant multifunctional polypeptides of the rapamycin (Rp)-producing polyketide synthase (RAPS1, RAPS2 and RAPS3) have recently been shown to contain 14 separate sets, or modules, of enzyme ... [more ▼]

The three giant multifunctional polypeptides of the rapamycin (Rp)-producing polyketide synthase (RAPS1, RAPS2 and RAPS3) have recently been shown to contain 14 separate sets, or modules, of enzyme activities, each module catalysing a specific round of polyketide chain extension. Detailed sequence comparison between these protein modules has allowed further characterisation of aa that may be important in catalysis or specificity. The acyl-carrier protein (ACP), beta-ketoacyl-ACP synthase (KS) and acyltransferase (AT) domains (the core domains) have an extremely high degree of mutual sequence homology. The KS domains in particular are almost perfect repeats over their entire length. Module 14 shows the least homology and is unique in possessing only core domains. The enoyl reductase (ER), beta-ketoacyl-ACP reductase (KR) and dehydratase (DH) domains are present even in certain modules where they are not apparently required. Four DH domains can be recognised as inactive by characteristic deletions in active site sequences, but for two others, and for KR and ER in module 3, the sequence is not distinguishable from that of active counterparts in other modules. The N terminus of RAPS1 contains a novel coenzyme A ligase (CL) domain that activates and attaches the shikimate-derived starter unit, and an ER activity that may modify the starter unit after attachment. The sequence comparison has revealed the surprisingly high sequence similarity between inter-domain 'linker' regions, and also a potential amphipathic helix at the N terminus of each multienzyme subunit which may promote dimerisation into active species. [less ▲]

Detailed reference viewed: 112 (2 UL)
Full Text
Peer Reviewed
See detailOrganisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of the enzymatic domains in the modular polyketide synthase
Aparicio, J. F.; Molnar, I.; Schwecke, T. et al

in Gene (1996), 169(1), 9-16

The three giant multifunctional polypeptides of the rapamycin (Rp)-producing polyketide synthase (RAPS1, RAPS2 and RAPS3) have recently been shown to contain 14 separate sets, or modules, of enzyme ... [more ▼]

The three giant multifunctional polypeptides of the rapamycin (Rp)-producing polyketide synthase (RAPS1, RAPS2 and RAPS3) have recently been shown to contain 14 separate sets, or modules, of enzyme activities, each module catalysing a specific round of polyketide chain extension. Detailed sequence comparison between these protein modules has allowed further characterisation of aa that may be important in catalysis or specificity. The acyl-carrier protein (ACP), beta-ketoacyl-ACP synthase (KS) and acyltransferase (AT) domains (the core domains) have an extremely high degree of mutual sequence homology. The KS domains in particular are almost perfect repeats over their entire length. Module 14 shows the least homology and is unique in possessing only core domains. The enoyl reductase (ER), beta-ketoacyl-ACP reductase (KR) and dehydratase (DH) domains are present even in certain modules where they are not apparently required. Four DH domains can be recognised as inactive by characteristic deletions in active site sequences, but for two others, and for KR and ER in module 3, the sequence is not distinguishable from that of active counterparts in other modules. The N terminus of RAPS1 contains a novel coenzyme A ligase (CL) domain that activates and attaches the shikimate-derived starter unit, and an ER activity that may modify the starter unit after attachment. The sequence comparison has revealed the surprisingly high sequence similarity between inter-domain 'linker' regions, and also a potential amphipathic helix at the N terminus of each multienzyme subunit which may promote dimerisation into active species. [less ▲]

Detailed reference viewed: 69 (2 UL)
Full Text
See detailDivergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases.
Haydock, S. F.; Aparicio, J. F.; König, Ariane UL et al

in FEBS Letters (1995), 374(2), 246-248

The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared ... [more ▼]

The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which the acyltransferase sequences diverged according to whether they were specific for malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to allow unambiguous assignment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the malonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase active site, though not close enough to make direct contact with bound substrate. [less ▲]

Detailed reference viewed: 86 (6 UL)
Full Text
Peer Reviewed
See detailThe biosynthetic cluster for the polyketide immunosuppressant rapamycin
Schwecke, T.; Aparicio, J. F.; Molnár, I. et al

in Proceedings of the National Academy of Sciences of the United States of America (1995), 92(17), 7839-7843

The macrocyclic polyketides rapamycin and FK506 are potent immunosuppressants that prevent T-cell proliferation through specific binding to intracellular protein receptors (immunophilins). The cloning and ... [more ▼]

The macrocyclic polyketides rapamycin and FK506 are potent immunosuppressants that prevent T-cell proliferation through specific binding to intracellular protein receptors (immunophilins). The cloning and specific alteration of the biosynthetic genes for these polyketides might allow the biosynthesis of clinically valuable analogues. We report here that three clustered polyketide synthase genes responsible for rapamycin biosynthesis in Streptomyces hygroscopicus together encode 14 homologous sets of enzyme activities (modules), each catalyzing a specific round of chain elongation. An adjacent gene encodes a pipecolate-incorporating enzyme, which completes the macrocycle. The total of 70 constituent active sites makes this the most complex multienzyme system identified so far. The DNA region sequenced (107.3 kbp) contains 24 additional open reading frames, some of which code for proteins governing other key steps in rapamycin biosynthesis. [less ▲]

Detailed reference viewed: 57 (3 UL)
See detailCloning of structural genes for type I polyketide synthases involved in macrolide polyether biosynthesis
König, Ariane UL; Schwecke, T.; Leadlay, P.F.

Scientific Conference (1994)

Detailed reference viewed: 54 (11 UL)