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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

One parameter frequently considered to be relevant for superspreading of trisiloxane surfactants is surface tension kinetics. In the scientific literature, some experimental results reported for trisiloxane surfactants are in contradiction with fundamental concepts of surfactant monomer diffusion. Therefore, maximum bubble pressure tensiometry has been used to determine dynamic surface tension (DST) of two types of trisiloxane surfactants: superspreader and non-superspreader. Results show that both surfactants behave similarly at concentrations below critical micelle concentration (CMC), as expected. The CMC curves, as determined by drop shape analysis, confirmed that the more hydrophilic non-superspreader has a higher CMC as compared to the more hydrophobic superspreader. Accordingly, the lower surfactant monomer concentration of the superspreader results in a higher DST than the non-superspreader at the same surface age. So, in contrary to claims in the literature, there is nothing mysterious or unexpected concerning the surface tension behavior of trisiloxane surfactants. Graphical Abstract

Tacrolimus is an immunosuppressant used in the treatment of people who have undergone organ and tissue transplants, as well as in the treatment of dermatoses and eye diseases. Strategies have been carried out to increase the productivity of tacrolimus, since many compounds have in their composition tacrolimus precursors, and bacteria Streptomyces depend on a carbon source for their growth. One strategy is to change the carbon source of the fermentation medium. The present study aims to evaluate the use of coconut oil for the production of tacrolimus via Streptomyces tsukubaensis, as an alternative in the face of glucose, a traditional source of carbon. The batch fermentation process was done in an orbital shaker at 28°C and 130 rpm. Quantification of tacrolimus was performed by High Performance Liquid Chromatography (HPLC). The sugars and proteins, present in the medium, were measured from Somogyi-Nelson and Bradford methods, respectively. According to the results, coconut oil achieved the production of tacrolimus higher than glucose. This is due to the presence of a portion of monounsaturated and polyunsaturated fatty acids that act as precursors to tacrolimus. On the other hand, glucose is a quick carbon source for the bacteria and helps in its growth, but in high amounts it inhibits the production of the drug.