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Optimizacija formulacije medijuma za proizvodnju antibiotika ciljanog delovanja primenom prirodnog izolata Streptomyces hygroscopicus / Optimization of media formulation for the production of antibiotics with target activity using the natural isolate Streptomyces hygroscopicus

<p style="text-align: justify;">Jedno od najvećih dostignuća u dvadesetom veku je bio pronalazak antibiotika i njihova primena u humanoj medicini. Međutim, vremenom se pokazalo da su izazivači bolesti mikroorganizmi koji &ldquo;uče&rdquo; i imaju sposobnost da se &ldquo;menjaju&rdquo;, &scaron;to neminovno dovodi do pojave antibiotske rezistencije, a čemu ide u prilog &scaron;iroko rasprostranjena upotreba antibiotika u lečenju pacijenata i primena humanih antimikrobnih lekova u veterini i fitofarmaciji. Razvoj novih i unapređenje postojećih farmaceutika zahteva ogromna ulaganja koja se mogu ali i ne moraju vratiti godinama. Prvi korak u razvoju novog farmaceutika je identifikacija ciljanog antibiotskog delovanja metabolita izabranog proizvodnog mikroorganizma, nakon čega sledi optimizacija uslova biosinteze u smislu sastava medijuma za proizvodnju.<br />Osnovni cilj ove doktorske disertacije je optimizacija formulacije medijuma za kultivaciju prirodnog izolata Streptomyces hygroscopicus u pogledu izvora makronutrijenata i njihovih količina, kako bi se metabolička aktivnost primenjenog proizvodnog mikroorganizma, u definisanim proizvodnim uslovima, usmerila ka sintezi antibiotika sa ciljanim delovanjem.<br />Optimizacijom formulacije medijuma za kultivaciju prirodnog izolata <em>Streptomyces hygroscopicus</em>, u primenjenim eksperimentalnim uslovima, odabrani su najpogodniji izvori makronutrijenata i definisane su njihove optimalne koncentracije za proizvodnju antibiotika sa ciljanim delovanjem. Utvrđeno je da je biosinteza baktericida efikasnih protiv <em>B. cereus</em> ATCC 10876, <em>S. aureus</em> ATCC 11632 i P. <em>aeruginosa</em> ATCC 27853 najizraženija u medijumu sa fruktozom, sojinim bra&scaron;nom i fosfatnim solima, dok je za dobijanje fungicida koji deluju na <em>C. albicans</em> ATCC 10231 i <em>A. niger</em> ATCC 16404 najadekvatnije primeniti medijum sa glukozom kao izvorom ugljenika i već pomenutim izvorima azota i fosfora pri čemu je odnos navedenih sastojaka medijuma specifičan za svaki test mikroorganizam. Sa tehnolo&scaron;kog aspekta, rezultati ovih istraživanja predstavljaju pouzdan izvor informacija za unapređenje proizvodnih karakteristika primenjenog biokatalizatora, izbor tehnike kultivacije, definisanje toka i optimizaciju postupka proizvodnje baktericida i fungicida sa krajnjim ciljem uvećanja razmera posmatranog bioprocesa.</p> / <p>One of the greatest achievements in the twentieth century was the invention of antibiotics and their application in human medicine. However, over time, it has been proven that disease susceptors are &quot;learning&quot; microorganisms and have the ability to &quot;change&quot;, which inevitably leads to the emergence of antibiotic resistance, which is in favor of widespread use of antibiotics in the treatment of patients and the application of human antibiotics in veterinary medicine and phytopharmacy. The development of new and the advancement of existing pharmaceuticals requires huge investments that may or may not be back for years. The first step in the development of a new pharmaceutical is the identification of the target antibiotic activity of the metabolite of the selected production microorganism, followed by the optimization of the conditions of biosynthesis in terms of composition of the production medium.<br />The main goal of this PhD thesis is the optimization of the formulation of the medium for the cultivation of the natural isolate Streptomyces hygroscopicus in terms of the source of macronutrients and their amounts, in order to direct the metabolic activity of the applied production microorganism, in the defined production conditions, towards the synthesis of antibiotics with targeted action. By optimizing the formulation of the medium for the culture of the natural isolate Streptomyces hygroscopicus, in the applied experimental conditions, the most suitable sources of macronutrients were selected and their optimal concentrations for the production of antibiotics with targeted action were defined. The biosynthesis of bactericides was found to be effective against B. cereus ATCC 10876, S. aureus ATCC 11632 and P. aeruginosa ATCC 27853 most pronounced in the medium with fructose, soy flour and phosphate salts, while for the production of fungicides acting on C. albicans ATCC 10231 and A. niger ATCC 16404 most appropriately apply a glucose medium as carbon source and already mentioned sources of nitrogen and phosphorus wherein the ratio of said ingredients to the medium is specific to each test microorganism. From a technological point of view, the results of these studies represent a reliable source of information for improving the production characteristics of the applied biocatalyst, a selection of cultivation techniques, defining the flow and optimizing the production of bactericides and fungicides with the ultimate goal of increasing the size of the observed bioprocess.</p>

Identiferoai:union.ndltd.org:uns.ac.rs/oai:CRISUNS:(BISIS)108239
Date01 March 2019
CreatorsVeličković Tatjana
ContributorsDodić Jelena, Grahovac Jovana, Rončević Zorana, Savić Dragiša
PublisherUniverzitet u Novom Sadu, Tehnološki fakultet Novi Sad, University of Novi Sad, Faculty of Technology at Novi Sad
Source SetsUniversity of Novi Sad
LanguageSerbian
Detected LanguageEnglish
TypePhD thesis

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