Submitted by Morgana Silva (morgana_linhares@yahoo.com.br) on 2016-09-26T17:37:22Z No. of bitstreams: 1 arquivototal.pdf: 1528163 bytes, checksum: 23433094cbc38f739e3ad5889cdc6092 (MD5) / Made available in DSpace on 2016-09-26T17:37:23Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1528163 bytes, checksum: 23433094cbc38f739e3ad5889cdc6092 (MD5) Previous issue date: 2016-02-29 / The dissertation has as its theme the capture of the regulator, in particular the Regulatory Agencies implemented in the legal system from the American model with the administrative reform carried out with more emphasis in the government of Fernando Henrique Cardoso. In this reform, the regulatory agencies have been placed as a modern model and legal certainty generator, considering that their leaders, because they are technical professionals in the regulated area, would be more protected from outside influence, and thus harder to regulatory capture. Notwithstanding the model "modern" presented the facts demonstrated the capture of leaders of regulatory agencies, not fulfilling these ones promised in the administrative reform of the 1990s in Brazil. They will be analyzed in the first chapter, the historical and economic assumptions of regulatory agencies; in the second chapter, it analyzes will be the regulatory agencies, and in the latter the phenomenon of regulatory capture of the agencies. From the combination of the theoretical framework of the Theory of Economic Regulation (economic theory of capture), George J. Stigler, and the notion of State from Leon Duguit, state-fact theory, the conclusion about the capture of the dynamics will be made of specific regulatory entities, called Independent Regulatory Agencies. / A dissertação tem como tema a captura do agente regulador, em especial das Agências Reguladoras implementadas no ordenamento jurídico a partir do modelo norte-americano com a reforma administrativa realizada com mais ênfase no governo de Fernando Henrique Cardoso. Nessa reforma, as Agências Reguladoras foram colocadas como um modelo moderno e gerador de segurança jurídica, haja vista que os seus dirigentes, por serem profissionais técnicos na área regulada, estariam mais protegidos da influência externa, sendo, assim, mais difícil a captura regulatória. Não obstante o modelo “moderno” apresentado, os fatos demonstraram a captura dos dirigentes das Agências Reguladoras, não cumprindo esses entes o prometido na reforma administrativa da década de 1990 no Brasil. Serão analisados, no primeiro capítulo, os pressupostos históricos e econômicos das Agências Reguladoras; no segundo capítulo, analisarse- ão as Agências Reguladoras, e, no último o fenômeno da captura regulatória das agências. A partir da conjugação dos referenciais teóricos da Teoria da Regulação Econômica (teoria econômica da captura), de George J. Stigler, e da noção de Estado de León Duguit, teoria do Estado-fato, será feita a conclusão acerca da dinâmica da captura dos entes regulatórios específicos, denominados de Agências Reguladoras Independentes.

Background: Subtilin is a peptide antibiotic (lantibiotic) natively produced by Bacillus subtilis ATCC6633. It is encoded in a gene cluster spaBTCSIFEGRK (spa-locus) consisting of four transcriptional units: spaS (subtilin pre-peptide), spaBTC (modification and export), spaIFEG (immunity) and spaRK (regulation). Despite the pioneer understanding on subtilin biosynthesis, a robust platform to facilitate subtilin research and improve subtilin production is still a poorly explored spot. Results: In this work, the intact spa-locus was successfully integrated into the chromosome of Bacillus subtilis W168, which is the by far best-characterized Gram-positive model organism with powerful genetics and many advantages in industrial use. Through systematic analysis of spa-promoter activities in B. subtilis W168 wild type and mutant strains, our work demonstrates that subtilin is basally expressed in B. subtilis W168, and the transition state regulator AbrB strongly represses subtilin biosynthesis in a growth phase-dependent manner. The deletion of AbrB remarkably enhanced subtilin gene expression, resulting in comparable yield of bioactive subtilin production as for B. subtilis ATCC6633. However, while in B. subtilis ATCC6633 AbrB regulates subtilin gene expression via SigH, which in turn activates spaRK, AbrB of B. subtilis W168 controls subtilin gene expression in SigH-independent manner, except for the regulation of spaBTC. Furthermore, the work shows that subtilin biosynthesis in B. subtilis W168 is regulated by the two-component regulatory system SpaRK and strictly relies on subtilin itself as inducer to fulfill the autoregulatory circuit. In addition, by incorporating the subtilin-producing system (spa-locus) and subtilin-reporting system (PpsdA-lux) together, we developed “online” reporter strains to efficiently monitor the dynamics of subtilin biosynthesis. Conclusions: Within this study, the model organism B. subtilis W168 was successfully established as a novel platform for subtilin biosynthesis and the underlying regulatory mechanism was comprehensively characterized. This work will not only facilitate genetic (engineering) studies on subtilin, but also pave the way for its industrial production. More broadly, this work will shed new light on the heterologous production of other lantibiotics.