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Title:Izboljšanje stabilnosti fermentacijske brozge klavulanske kisline pred izolacijo z optimiranjem procesnih parametrov : magistrsko delo
Authors:ID Zadravec, Simon (Author)
ID Knez Marevci, Maša (Mentor) More about this mentor... New window
Files:.pdf MAG_Zadravec_Simon_2025.pdf (5,04 MB)
MD5: 7AE713E3286C64513A06F53DA9A6C406
 
Language:Slovenian
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:FKKT - Faculty of Chemistry and Chemical Engineering
Abstract:Bakterija Streptomyces clavuligerus med fermentacijskim procesom sintetizira klavulansko kislino (KK), ki učinkovito deluje kot inhibitor β-laktamaz in se uporablja v kombinaciji z antibiotiki za premagovanje bakterijske odpornosti. Nestabilnost KK med proizvodnim procesom predstavlja velik izziv, saj hitro razpada, kar zmanjšuje izkoristek in povečuje stroške proizvodnje. Namen te študije je izboljšati biosintezo KK z osredotočanjem na preučevanje vpliva procesnih parametrov na njeno stabilnost in produkcijo. V magistrskem delu smo razvili kvantitativni spektrometrični model za merjenje koncentracij KK in glicerola. Razvit model omogoča hitro, učinkovito in robustno analizo teh dveh spojin med eksperimentalnimi poskusi, kar predstavlja izboljšanje v primerjavi s klasičnimi kromatografskimi tehnikami, saj pospeši pridobivanje rezultatov. Model smo nato uporabili za spremljanje koncentracij KKin glicerola med eksperimentalnimi poskusi, v katerih smo spreminjali različne procesne parametre, kot so mešanje, zračenje, nadtlak, temperatura, redčenje ter kombinirali brozge iz različnih faz produkcijskega cikla S. clavuligerus. Poleg tega smo merili tudi koncentracijo raztopljenega kisika, viskoznost, pH in prisotnost nečistoče A, ki je razgradni produkt klavulanske kisline. Rezultati so pokazali, da lahko pravilna nastavitev procesnih parametrov bistveno izboljša stabilnost in produktivnost klavulanske kisline. Povečanje zračenja in mešanja ter zvišanje tlaka je prineslo do 5 % izboljšanje izkoristka po 6 urah zadrževalnega časa ter 17 % izboljšanje izkoristka po 27 urah procesa, hkrati pa je koncentracija nečistoče A ostala stabilna, kar kaže na manjšo razgradnjo KK. Posamezno povečanje mešanja, zračenja ali tlaka ni dalo enako učinkovitih rezultatov, čeprav je prispevalo k zmanjšanju razgradnje KK od 11 % do 26 %. Ugotovitve prispevajo k optimizaciji industrijskega procesa proizvodnje KK, saj zmanjšujejo razgradnjo produkta in povečujejo izkoristek, kar vodi v bolj učinkovit proces in nižje stroške proizvodnje.
Keywords:klavulanska kislina, fermentacijski proces, stabilnost, optimizacija procesnih parametrov, spektrometrija
Place of publishing:Maribor
Place of performance:Maribor
Publisher:[S. Zadravec]
Year of publishing:2025
Number of pages:1 spletni vir (1 datoteka PDF (XI, 72 str.))
PID:20.500.12556/DKUM-90899 New window
UDC:66.011:604.4(043.2)
COBISS.SI-ID:229007107 New window
Publication date in DKUM:28.02.2025
Views:248
Downloads:60
Metadata:XML DC-XML DC-RDF
Categories:KTFMB - FKKT
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Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:02.10.2024

Secondary language

Language:English
Title:Enhancement of clavulanic acid fermentation broth stability before downstream operations by optimization of process parameters
Abstract:During the fermentation process, the bacterium Streptomyces clavuligerus synthesises clavulanic acid (CA), which acts effectively as an inhibitor of β-lactamases and is used in combination with antibiotics to overcome bacterial resistance. The instability of CA during the production process poses a major challenge as it degrades rapidly, reducing yields and increasing production costs. The aim of this study is to improve the biosynthesis of CA by focusing on the study of the influence of process parameters on its stability and production. In this Master thesis, a quantitative spectrometric model was developed to measure the concentrations of CA and glycerol. The developed model allows a fast, efficient and robust analysis of these two compounds during experimental trials, which is an improvement over classical chromatographic techniques as it speeds up the acquisition of results. The model was then used to monitor the concentrations of CA and glycerol during experimental trials in which different process parameters such as agitation, aeration, overpressure, temperature, dilution were varied and broths from different stages of the S. clavuligerus production cycle were combined. In addition, dissolved oxygen concentration, viscosity, pH and the presence of impurity A, a degradation product of CA, were measured. The results showed that the correct adjustment of process parameters can significantly improve the stability and productivity of CA. Increasing aeration and agitation and increasing the pressure resulted in up to a 5 % improvement in yield after 6 hours of residence time and a 17 % improvement in yield after 27 hours of the process, while the concentration of impurity A remained stable, indicating a lower degradation of the CA. Individual increases in agitation, aeration or pressure did not give the same effective results, although they contributed to a reduction in CA degradation of between 11 % and 26 %. The findings contribute to the optimisation of the industrial CA production process by reducing product degradation and increasing recovery, leading to a more efficient process and lower production costs.
Keywords:clavulanic acid, fermentation process, stability, optimization of process parameters, spectroscopy


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