Use of three-carbon chain compounds as biosynthesis precursors to enhance tacrolimus production in Streptomyces tsukubaensis

Gajzlerska, Wanda; Kurkowiak, Justyna; Turło, Jadwiga

doi:10.1016/j.nbt.2014.07.006

Cited by 13 publications

(5 citation statements)

References 25 publications

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“…Precursors such as malonyl -COA, DHCHC, methylmalonyl -CoA, allymalonyl -CoA, methoxylmalonyl ACP synthesized in these pathways help for tacrolimus production [4]. Moreover, three -carbon compounds such as propylene glycol, propanol, or propionic acid promote the growth of S. tsukubaensis and eventually increase tacrolimus production [21].…”

Section: Metabolic Regulation Through Supplementation Of Various Comp...mentioning

confidence: 99%

Tacrolimus: Strategies to Improve Tacrolimus Production at Classical and Transcriptional Levels

2022

JCMP

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Tacrolimus (FK506) is a 23 membered polyketide macrolide, a potent immunosuppressant, and a useful secondary metabolite that exhibits 10 -100 times more efficient than cyclosporine. It becomes an important therapeutic drug not only in transplantation but also used frequently in the treatment of severe atopic dermatitis, and secondary lymphedema. Biosynthesis of Tacrolimus is a multifaceted process involved in many essential pathways, but low productivity of tacrolimus fromStreptomyces sp. is a major concern regarding its increased global demand. To boost Tacrolimus production, many steps such as alteration in the biosynthetic pathway, strain improvements, optimizing culture conditions, and use of tacrolimus precursors have been adapted. This review focuses on different approaches at the nutritional and genetic engineering level to scale up the titer of tacrolimus.

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Section: Metabolic Regulation Through Supplementation Of Various Comp...mentioning

confidence: 99%

Tacrolimus: Strategies to Improve Tacrolimus Production at Classical and Transcriptional Levels

2022

JCMP

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“…At the present time, the large-scale industrial production of tacrolimus is based on the fermentation broth of various Streptomyces species cultivated in submerged cultures [91][92][93][94][95][96][97][98][99][100][101]. As a result of high production cost and low yield, the cost of tacrolimus pharmacotherapy is very high.…”

Section: Tacrolimus-prografmentioning

confidence: 99%

Immunopharmacological Drugs

Vardanyan

Hruby

2016

Synthesis of Best-Seller Drugs

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“…The filtered solution obtained is subjected to several adsorption steps, whose stationary phases are conventional resins and/or conventional adsorbents, such as silica gel, activated carbon (DUMONT et al, 1992), using elution with conventional solvents, as n-hexane, ethyl acetate (KINO et al, 1987), tetrahydrofuran (THF), acetone, acetonitrile (ACN), ethanol and isopropanol (KERI et al, 2006). Some studies describe important steps in the process of obtaining the drug, aiming at its purification without, however, going into details regarding the biomass filtration step (micelles) (JUNG et al, 2011;GAJZLERSKA et al, 2015). Other studies, after obtaining the fermented broth, mention the quantification of tacrolimus, via liquid chromatography and omitting the removal of micelles (VAID, 2007;MISHRA and VERMA, 2012;TRIPATHI et al, 2014;MO and YANG, 2016).…”

Section: Tacrolimus and Its Obtainingmentioning

confidence: 99%

Microfiltration of micelles from fermentation of "Streptomyces tsukubaensis" for the production of tacrolimus

Suzin Bertan

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Tacrolimus is a drug recommended as immunosuppressant for kidney and liver transplant therapy, treatment of autoimmune diseases, rheumatoid arthritis and lichen planus, as well as in the treatment of bronchial asthma, dermatological disorders such as vitiligo, psoriasis, atopic dermatitis, eye diseases such as uveitis and in the treatment of patients with idiopathic membranous nephropathy. This Dissertation aims to improve the tacrolimus recovery process through the development of a pressurized column for fermented broth microfiltration from fermentation via Streptomyces tsukubaensis, which contains tacrolimus, so that the micelles present in the broth are retained with 95 % rejection at least. Fermentation runs were carried out using coconut oil and glucose as carbon sources, obtaining the specific production of the drug equal to 1.88 mg/g and 1.69 mg/g, respectively. In addition to identifying and quantifying the drug, it was possible to quantify the biomass, sugars, and proteins from fermentation. In view of the need to evaluate the performance of the proposed system, addressed to the removal of micelles, an alternative technique was developed that associates the particle counting by the Neubauer chamber with the spectroscopy technique, making it possible to associate the number of particles with the absorbance. In addition, a study was carried out on the rheology of raw broth fermented with acetone submitted to microfiltration, verifying non-Newtonian behavior, of a pseudoplastic nature, significantly for temperatures above 30 °C. Regarding the performance of microfiltration, the performance of two membranes, 0.22 µm and 3.00 µm of average pore diameter, were subjected to operating pressures of 1 bar and 2 bar. It was found that a simple batch of microfiltration was not enough to achieve 95 % removal. Thus, the strategy of multiple steps of the permeate through the filter was established, obtaining the desired removal in 6 passages, and the maximum rejection obtained from the micelle was 97%, achieved in ten steps. This performance was achieved with 3.00 µm membrane, using 1 bar operating pressure. It was observed that the permeate volumetric flow decreases with the increase in the steps number until it remains constant. This behavior is observed with the total resistance of the filter medium, which remains constant after a certain step, but, before, the total resistance increases with the steps number. It should be noted that, given the scope of the application of tacrolimus and its distribution by the Brazilian Unified Health System (SUS), the dimension of its production for society was contextualized, emphasizing the importance of hope as essential element in the chemical project of obtaining of the drug, concluding that it is possible to do science and develop innovative technology with a strong social commitment.

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Use of three-carbon chain compounds as biosynthesis precursors to enhance tacrolimus production in Streptomyces tsukubaensis

Cited by 13 publications

References 25 publications

Tacrolimus: Strategies to Improve Tacrolimus Production at Classical and Transcriptional Levels

Tacrolimus: Strategies to Improve Tacrolimus Production at Classical and Transcriptional Levels

Immunopharmacological Drugs

Microfiltration of micelles from fermentation of "Streptomyces tsukubaensis" for the production of tacrolimus

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