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Introduction Tacrolimus, also known as FK-506, is a drug first isolated in 1984, that has been widely used to prevent the rejection of transplanted organs, and to also treat dermatoses and eye diseases. 1-3 It is a 23 membered polyketide macrolide produced during fermentation through different Streptomyces species. The most commonly used is the Streptomyces tsukubaensis. 4 This medication is interesting to dermatology because it is rapidly absorbed by the epidermis and has less side effects than commonly used drugs. 5 Besides, as an immunosuppressant agent it is 10-100 times more potent than cyclosporine. 6 Nevertheless, the treatment cost using tacrolimus is high because of its low productivity. 7 Up to now, different strategies have been used to solve this problem, including the use of mutant bacteria, 8-11 and exogenous feeding of precursors in the biosynthesis. 12-14 Literature reports that S. tsukubaensis is capable of metabolizing different carbon sources, such as glucose, maltose, dextrin, soybean oil, cottonseed oil and groundnut oil. 14-16 Exogenous feeding of oil has played an important role in this bioprocess, since it is a complex source of nutrients which has increased the tacrolimus production. 12,14,17 The Brazil nut oil is rich in fatty acids and are broken in order to produce coenzymes (acetyl or propionyl) which are known as precursors for the polyketide production. 17 This study has investigated the influence of the Brazil nut (Bertholletia excelsa) oil on the tacrolimus production. The fermentative process was carried for 168 h using S. tsukubaensis. Materials and Methods Organism The Strain of S. tsukubaensis was acquired from the Leibniz Institute DSMZ. Culture Conditions Streptomyces tsukubaensis culture was maintained on petri dishes containing glucose 4 g.L-1 , yeast extract 1 g.L-1 , malt extract 10 g.L-1 , CaCO 3 2 g.L-1 and agar 12 g.L-1 , pH 7.2, and incubated at 28 o C. The seed culture medium and the production medium were based on Turlo et al 14 which are presented in Table 1 and Table 2, respectively. The seed culture medium was prepared, sterilized at 120 o C

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), also known for its significant antipyretic and analgesic properties. This chiral drug is commercialized in racemic form; however, only S-(+)-ibuprofen has clinical activities. In this paper the effect of temperature change (from 288.15 to 308.15 K) on the ibuprofen resolution was studied. A column (250×4.6 mm) packed with tris(3,5-dimethylphenylcarbamate) was used to obtain the thermodynamic parameters, such as enthalpy change (ΔH), entropy change (ΔS), variation enthalpy change (ΔΔH), variation entropy change (ΔΔS), and isoenantioselective temperature (Tiso). The mobile phase was a combination of hexane (99%), isopropyl alcohol (1%), and TFA (0.1%), as an additive. The conditions led to a selectivity of 1.20 and resolution of 4.55. The first peak, R-(−)-ibuprofen, presented an enthalpy change of 7.21 kJ/mol and entropy change of 42.88 kJ/K·mol; the last peak, S-(+)-ibuprofen, has an enthalpy change of 8.76 kJ/mol and 49.40 kJ/K·mol of entropy change.

Agradeço imensamente ao meu pai, Jorge Moreira, pela ajuda, incentivo e apoio que me concedeu, desde o começo. Sempre esperando meu melhor. Espero que eu tenha atendido suas expectativas.A minha mãe e irmã, Sueli Maciel e Jéssica Moreira, por todas as conversas, risadas e tempos de descontração, embora não nos vejamos com muita frequência, sempre estaremos ligados pelos laços da amizade e amor.Aos meus avós, Lauro Maciel de Souza e Maria Lopes de Souza serão sempre para mim um exemplo e donos dos meus melhores momentos.Ao professor Marco Aurélio Cremasco pela oportunidade do trabalho e experiência de trabalhar com algo diferente, pela orientação e disposição que teve comigo.Aos meus amigos, que de uma maneira, às vezes imperceptível me ajudaram tanto.Mesmo correndo o risco de esquecer alguém, seria injusto não nomeá-los,

Agradeço imensamente ao meu pai, Jorge Moreira, por todo o inventivo nestes anos, pelo apoio e encorajamento em todos os momentos.À minha mãe e irmã, Sueli Maciel e Jéssica Moreira, pois sei que ambas torcem e esperam o meu melhor sempre. Espero nunca decepcioná-las.Aos meus avós, Lauro e Maria Lopes de Souza, que são exemplos de vida e superação a seguir.À Mayara Braga, por todos os bons momentos compartilhados, incentivo, e por ter sido sempre uma voz de apoio em tempos conturbados.